tag:blogger.com,1999:blog-33960805Fri, 11 Aug 2017 15:23:41 +0000marketingZyprexaantipsychotickey opinion leaderSeroquelLillystealth marketingantidepressantsdepressionchild bipolarbipolar disorderAstraZenecaolanzapineoff-label marketingsuicideAbilifyPaxilscienceNemeroffRisperdalGlaxoSmithKlinecontinuing medical educationconflict of interestFurious SeasonsSeroxatsuppressionghostwritingquetiapineCymbaltaMartin KellerPfizerSSRIVioxxjournalsEffexorPharmaGilesSSRIsbiasLisa Blakemore BrownPeter Rostacademic medicineARISE-RD studyCorceptFDAJanssenScientific Misconduct BlogdementiadiabetesmisconductschizophreniaCorluxDaniel CarlatDrug WonksHealth Care RenewalMerckPristiqThe Last Psychiatristcash moneymifepristonepeer reviewpseudoevidence based medicineAmerican Psychological AssociationBritish Psychological SocietyDSMEvidenceInvegaanxietyblogschemical imbalancegeneralized anxietylawsuityellow journalismAstroturfingBMSBOLDERBrandweekCurrent PsychiatryJohn MackKrusty the KlownNeuroneticsPanoramaPharma BlogospherePhilip DawdyProcter and GambleWTFWyethZoloftand Zyprexachildrendoggie Prozaclawyersmediaparanoiapublic relationspublication processsocial anxietyADHDAvandiaBen HansenChristopher LaneCovington and BurlingDavid HealyDecision ResourcesDepakoteForestFred HassanGeneral Medical CouncilGeodonGoogleJohnson and JohnsonJournal of Clinical PsychiatryLexaproMAOINAMINational Health ServicePharmaGossipPharmalotRita PalSiegfried KasperTMAPThinking Blogger AwardWiki ScannerZetiaasenapinebeyond descriptionbifeprunoxcorruptiondiagnosisduloxetineescitalopramglucoseherpeslamictallinksmedical educationplagiarismpoliticsrantsafety reportingsecrecytorturetranscranial magnetic stimulationAcompliaAlastiar BenbowAll in the MindAlliAndrew CutlerAnna Nicole SmithAnne TonkinArimidexAustralia Radio NationalBYUBig BrotherBill MaherBloggerBruegger's BagelsCelexaCephalonCesariniChuck DCongressConstant GardenerCyberonicsDSACDADDarth VaderDaubertDavid GrahamDemocratDepression AllianceEdelman PRExuberaFaruk AbuzzahabFiddamanFiona GodleeFlava FlavFumentoGabitrilGenotropinGooznerHannibalHavidolHenry WaxmanHookedImusIntueriJean FrazierJeffrey PeppercornJim EdwardsJohn GroholJon JureidiniKetekLipitorLunestaMarthaMasters of the UniverseMike BandickMina DuncanMolly IvinsMood Disorders QuestionnaireNIMHNew BloggerNicoretteObesity SocietyOperation Restore ConfidenceOrwellPaul KornakPepsiPrialtPsychCentralPsychSplashPublic EnemyRepublicanRichard SmithSchering-PloughSimpsonsSir Mix-A-LotSlateSpitzerSymbyaxT-DDDTACTexas Medication Algorithm ProjectTorVermontWally SmithYentreveaccountabilityagomelatineannoyancesanonymityanorexiaautismawardbenzodiazepinesbizarrebriberycaffeinecancer drugscheerleadercitalopramclonidinecopycatdeep brain stimulationdoublethinkdrug costsdrug repsdsm-veDrugSearcheditorsequal opportunityevil HTML tagsexecutive compensationexpertsgenericsgenetic testinggradinghilariousiloperidoneinsurancelegal inanitiesmmood stabilizersneurontinoverdoseparoxetinepatentpaternal agepayoffspolypharmacypsychosisracismreregulatorsresearchreviewreviewerssage wisdomsales representativesshenaniganssmoking cessationsubpoenasurveytreatmentvagus nerve stimulationwhistleblowingwhitewashingwhitwashingwithdrawalClinical Psychology and Psychiatry: A Closer LookPsychiatric medications, science, marketing, psychiatry in general, and occasionally clinical psychology. Questioning the role of key opinion leaders and the use of "science" to promote commercial ends rather than the needs of people with mental health concerns.http://clinpsyc.blogspot.com/noreply@blogger.com (CL Psych)Blogger692125tag:blogger.com,1999:blog-33960805.post-561695802826275206Wed, 23 Feb 2011 19:23:00 +00002011-02-23T11:24:28.688-08:00Alive But InactiveI just checked my blog email account for the first time in months. It's possible - not likely - that I will sort through the spam and actually read and reply to your emails. It's also possible and not likely that I will actually post something sometime in the next month or two.http://clinpsyc.blogspot.com/2011/02/alive-but-inactive.htmlnoreply@blogger.com (CL Psych)0tag:blogger.com,1999:blog-33960805.post-5419432012219692139Fri, 01 Oct 2010 18:13:00 +00002010-10-01T11:16:07.096-07:00antidepressantsCymbaltaEffexorSSRIsCymbalta and Effexor: Hype Over Science<span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;" id="internal-source-marker_0.1742055405244135"><span style="float: left; padding: 5px;"><a href="http://www.researchblogging.org"><img alt="ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png" style="border:0;" /></a></span></span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">Remember the hype around the serotonin-norepinephrine reuptake inhibitors (SNRIs)? Effexor and Cymbalta impact both serotonin </span><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: italic; text-decoration: none; vertical-align: baseline;">and</span><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> norepinephrine, so they should be more effective than SSRI’s in treating depression? Mind you, that’s not a high bar to clear - it’s not like SSRI’s are </span><a href="http://clinpsyc.blogspot.com/2008/02/antidepressants-meet-new-news-same-as.html"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">much better</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> than placebo. So get the hell outta the way, Prozac and Paxil, because Cymbalta and Effexor will unleash their incredible efficacy onto the world of psychiatry. Doubt me? Read this </span><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695227/"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">2009 article</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> regarding the wonders of Pristiq (son of Effexor) and learn about how “The emergence of the selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) antidepressants has improved the treatment of MDD.” Or this </span><a href="http://www.prnewswire.co.uk/cgi/news/release?id=57285"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">press release</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> from Wyeth. Or Dr. Danny Carlat’s experience </span><a href="http://carlatpsychiatry.blogspot.com/2007/11/dr-drug-rep.html"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">selling Effexor</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> to his peers. I don’t think anyone who has followed drug marketing would deny that both Wyeth and Lilly tried to pimp Effexor and Cymbalta as working better because of their SNRI properties. </span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"></span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">But is that actually true? A team of German researchers </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/20831742"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">examined the data</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> and concluded that neither Effexor nor Cymbalta really work better than SSRIs. They actually found a small advantage for Effexor over SSRIs for treatment response (but not depression remission), but they also found that the manufacturer was hiding studies from them (and the rest of the world). I haven’t said this for a while, but enter Charles Nemeroff. To understand the research by the Germans, we first need to recall that a </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/17888885?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">2008 study</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> (lead author: Nemeroff) found </span><br /><p style="margin-left: 36pt; margin-top: 0pt; margin-bottom: 0pt;"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">...the pooled effect size across all comparisons of venlafaxine versus SSRIs reflected an average difference in remission rates of 5.9%, which reflected a NNT of 17 (1/.059), that is, one would expect to treat approximately 17 patients with venlafaxine to see one more success than if all had been treated with another SSRI. Although this difference was reliable and would be important if applied to populations of depressed patients, </span><span style="font-size: 11pt; font-family: Arial; color: rgb(255, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">it is also true that it is modest and might not be noticed by busy clinicians in everyday practice.</span><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> </span><span style="font-size: 11pt; font-family: Arial; color: rgb(255, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">Nonetheless, an NNT of 17 </span><span style="font-size: 11pt; font-family: Arial; color: rgb(255, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">may be of public health relevance</span><span style="font-size: 11pt; font-family: Arial; color: rgb(255, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> given the large number of patients treated for depression and the significant burden of illness associated with this disorder. </span><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">[my emphasis]</span></p><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"></span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">As I wrote then, the benefit to public health claim is ridiculous. To understand the reasons why this is so laughable, please check out my </span><a href="http://clinpsyc.blogspot.com/2008/03/effexor-beats-ssris-kind-of-sort-of-in.html"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">prior post</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> on the topic. This meta-analysis included a bunch of data from Wyeth that was previously unpublished...<br /><br /></span><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">Which leads to the freshly published meta-analysis on how Effexor compares to SSRIs. The German researchers requested unpublished data from Wyeth and only got </span><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: italic; text-decoration: none; vertical-align: baseline;">some </span><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">of it - you’d think that just maybe Wyeth sent them the “good news” data and maybe held back on some of the “bad news” data. So when an ever-so-small benefit emerged for Effexor (5% high treatment response rate), well, call me crazy, but I ignored it. We’re not playing with a full dataset because the manufacturer wants to keep some of it hidden, so shame on Wyeth and let’s look at Effexor with a little bit of suspicion. So Effexor vs. SSRIs - no difference. Except that more people drop out of clinical trials on Effexor due to side effects compared to SSRIs (about 3% more). So even if you believe that Wyeth’s hidden data really doesn’t impact these findings, we’re left with a very small advantage for Effexor that is probably negated by its slightly higher dropout rates. </span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"></span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">Cymbalta. It had a 3% higher dropout rate due to adverse events and the same efficacy as SSRIs. So nothing to write home about, except that it costs a boatload more than generic SSRIs and is harder to tolerate. But Cymbalta has been marketed to the gills and is clearing </span><a href="http://www.reuters.com/article/idUSTRE67I4XG20100819"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">$3 billion</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> a year in sales. Hey, this is the company marketed Zyprexa for </span><a href="http://clinpsyc.blogspot.com/2007/02/demented-marketing-of-zyprexa.html"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">dementia</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> (</span><a href="http://clinpsyc.blogspot.com/2007/11/atypical-antipsychotics-for-elderly.html"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">oops</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">), and for, well, lots of other stuff (</span><a href="http://clinpsyc.blogspot.com/2007/02/zyprexa-off-label-marketing-part-2.html"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">1</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">, </span><a href="http://clinpsyc.blogspot.com/2007/02/zyprexa-off-label-promotion.html"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">2</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">). So it’s not surprising at all that they can take a mediocre antidepressant like Cymbalta and turn it into a big moneymaker - </span><a href="http://www.furiousseasons.com/archives/2008/06/cymbalta_the_swiss_army_knife_of_drugs.html"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">the wonders</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> of a good marketing department. But Depression Hurts and Cymbalta is a painkiller. Well, that’s fine and dandy until you actually look at the data which show Cymbalta </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/18087203"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">doesn’t do much</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"> for pain in depression. </span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"></span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">It’s time to get over the hype surrounding SNRIs. The next “advance” in antidepressants, well, who knows what it will be - but let’s hope it’s something a little more substantial than SNRIs. But I’m not hopeful. And no, I don’t want to hear anything more about </span><a href="http://clinpsyc.blogspot.com/search?q=agomelatine"><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 153); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: underline; vertical-align: baseline;">agomelatine</span></a><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">.</span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"></span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">I know it’s been a long time between posts. So pardon me if my writing is more awful than usual. And it doesn’t mean I will be posting regularly. Thanks to the multiple readers who sent me a copy of this article. </span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"></span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;">Citation to new meta-analysis of Effexor and Cymbalta:</span><br /><span style="font-size: 11pt; font-family: Arial; color: rgb(0, 0, 0); background-color: transparent; font-weight: normal; font-style: normal; text-decoration: none; vertical-align: baseline;"><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Acta+Psychiatrica+Scandinavica&amp;rft_id=info%3Adoi%2F10.1111%2Fj.1600-0447.2010.01599.x&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=A+systematic+review+of+duloxetine+and+venlafaxine+in+major+depression%2C+including+unpublished+data&amp;rft.issn=0001690X&amp;rft.date=2010&amp;rft.volume=&amp;rft.issue=&amp;rft.spage=0&amp;rft.epage=0&amp;rft.artnum=http%3A%2F%2Fdoi.wiley.com%2F10.1111%2Fj.1600-0447.2010.01599.x&amp;rft.au=Schueler%2C+Y.&amp;rft.au=Koesters%2C+M.&amp;rft.au=Wieseler%2C+B.&amp;rft.au=Grouven%2C+U.&amp;rft.au=Kromp%2C+M.&amp;rft.au=Kerekes%2C+M.&amp;rft.au=Kreis%2C+J.&amp;rft.au=Kaiser%2C+T.&amp;rft.au=Becker%2C+T.&amp;rft.au=Weinmann%2C+S.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Health%2CPsychiatry">Schueler, Y., Koesters, M., Wieseler, B., Grouven, U., Kromp, M., Kerekes, M., Kreis, J., Kaiser, T., Becker, T., &amp; Weinmann, S. (2010). A systematic review of duloxetine and venlafaxine in major depression, including unpublished data <span style="font-style: italic;">Acta Psychiatrica Scandinavica</span> DOI: <a rev="review" href="http://dx.doi.org/10.1111/j.1600-0447.2010.01599.x">10.1111/j.1600-0447.2010.01599.x</a></span></span>http://clinpsyc.blogspot.com/2010/10/cymbalta-and-effexor-hype-over-science.htmlnoreply@blogger.com (CL Psych)5tag:blogger.com,1999:blog-33960805.post-5849301876096111136Fri, 14 May 2010 15:18:00 +00002010-05-14T08:20:06.985-07:00antidepressantsjournalsLillyscienceEli Lilly: Our Drug Failed, So it Has Serious Potential<span style="float: left; padding: 5px;"><a href="http://www.researchblogging.org"><img alt="ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png" style="border:0;" /></a></span><br />These folks at Lilly must think we are exceptionally stupid. As in can't tie our own shoes. A study in the Journal of Psychiatric Research recently found that their experimental antidepressant LY2216684 was no better than placebo. Here are a couple of quotes from the abstract:<br /><blockquote>LY2216684 did not show statistically significant improvement from baseline compared to placebo in the primary analysis of the Hamilton depression rating scale (HAM-D17) total score. Escitalopram demonstrated significant improvement compared to placebo on the HAM-D17 total score, suggesting adequate assay sensitivity.<br /></blockquote>On the primary outcome measure, the experimental drug failed whereas Lexapro worked to some extent. I know what you're thinking - "the sample size was probably too small to find a significant effect." Um, you're wrong. How about 269 people on the Lilly drug, 138 on placebo, and 62 on Lexapro.<br /><br />But wait, here comes the good news...<br /><blockquote>Both LY2216684 and escitalopram showed statistically significant improvement from baseline on the patient-rated QIDS-SR total score compared to placebo... The results of this initial investigation of LY2216684’s efficacy suggest that<span style="color:#ff0000;"> it may have antidepressant potential.</span><br /></blockquote>The good news for Lilly is that most people who claim to "read journal articles" really just browse the abstract without actually looking at the full text of the paper. For the select few who have nothing better to do than read Lilly propaganda, take a look at Table 2. A total of 12 secondary outcome measures are listed. The Lilly drug beat placebo on... ONE of them. Lilly doesn't say much about how much better their drug was than placebo on the QIDS-SR measure beside throwing around that often meaningless term of "statistically significant." People on the drug improved by 10.2 points whereas placebo patients improved 8.3 points. So about a 20% difference. If you bother to calculate an effect size, it is d = .24, which is quite small and clinically insignificant. So on the ONE measure where the drug was better than placebo, it was by a small margin, and it missed the mark on 11 other secondary measures as well as on the primary outcome measure. But "it may have antidepressant potential." Hell yes, I've never been so exited about a new drug.<br /><br />By the way, Lilly is apparently trying this wonder drug out in at least <a href="http://clinicaltrials.gov/ct2/results?term=LY2216684" id="yidi" title="five trials">five trials</a>. The journal in which this article appeared has published other <a href="http://clinpsyc.blogspot.com/2008/09/cymbalta-schatz-storm-duplicate.html" id="ek6v" title="dubious Eli Lilly research">dubious Eli Lilly research</a> in the past. The editorial review process is clearly working wonders over at the Journal of Psychiatric Research. Sad, really. The journal publishes some really good work, but then runs this kind of junk as well.<br /><br /><b>Depression Self-Report Sidebar: </b>The self-reported measure on which the drug had an advantage, the Quick Inventory of Depressive Symptoms (QIDS) - it's really awesome, according to Lilly. Remember, it's the only measure on which their experimental <strike>failure</strike> drug had an advantage over placebo. So the authors wrote "Self-reported depression symptoms, such as those obtained by the QIDS-SR, may be more sensitive than clinician-administered scales for signal detection in clinical studies of depression."<br /><br />What does Bristol-Myers Squibb think? In three trials of Abilify for depression, self-reports of depression were unfavorable. So the publications for these studies made sure to downplay these depression self-reports by saying that these measures were <a href="http://clinpsyc.blogspot.com/2009/01/abilify-for-depression-im-not-only.html" id="f86x" title="not sensitive">not sensitive</a>, that they weren't picking up improvements in depression.<br /><br />So if a self-report provided positive results, then BAM, it's an awesome measure of depression. But if it provided negative results, then it's a horrendously inaccurate measure and should never have been used in the first place.<br /><br />Citation below. Yes, one of the authors' last names is Kielbasa.<br /><br /><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Journal+of+Psychiatric+Research&amp;rft_id=info%3Adoi%2F10.1016%2Fj.jpsychires.2009.09.013&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=A+study+of+the+effects+of+LY2216684%2C+a+selective+norepinephrine+reuptake+inhibitor%2C+in+the+treatment+of+major+depression&amp;rft.issn=00223956&amp;rft.date=2010&amp;rft.volume=44&amp;rft.issue=6&amp;rft.spage=356&amp;rft.epage=363&amp;rft.artnum=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0022395609002131&amp;rft.au=Dub%C3%A9%2C+S.&amp;rft.au=Dellva%2C+M.&amp;rft.au=Jones%2C+M.&amp;rft.au=Kielbasa%2C+W.&amp;rft.au=Padich%2C+R.&amp;rft.au=Saha%2C+A.&amp;rft.au=Rao%2C+P.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Health%2CPsychiatry">Dubé, S., Dellva, M., Jones, M., Kielbasa, W., Padich, R., Saha, A., &amp; Rao, P. (2010). A study of the effects of LY2216684, a selective norepinephrine reuptake inhibitor, in the treatment of major depression <span style="font-style: italic;">Journal of Psychiatric Research, 44</span> (6), 356-363 DOI: <a rev="review" href="http://dx.doi.org/10.1016/j.jpsychires.2009.09.013">10.1016/j.jpsychires.2009.09.013</a></span>http://clinpsyc.blogspot.com/2010/05/eli-lilly-our-drug-failed-so-it-has.htmlnoreply@blogger.com (CL Psych)13tag:blogger.com,1999:blog-33960805.post-1498938453147080677Fri, 02 Apr 2010 19:16:00 +00002010-04-02T12:29:14.076-07:00Charles Nemeroff, Consultant ExtraordinaireThe key opinion leader of key opinion leaders. Or <a href="http://books.google.com/books?id=5w64WC_-jbMC&amp;pg=PT225&amp;lpg=PT225&amp;dq=nemeroff+boss+bosses&amp;source=bl&amp;ots=nn13_My3aH&amp;sig=wNUgi6D4DTqiGdM75pvNx5LTZMs&amp;hl=en&amp;ei=yUS2S9KtJJKmngfXy-iJDQ&amp;sa=X&amp;oi=book_result&amp;ct=result&amp;resnum=9&amp;ved=0CCAQ6AEwCDgK">Boss of Bosses</a>, if you prefer. In any case, take a peek at the following from Charles Nemeroff's page on the University of Miami's <a href="http://psychiatry.med.miami.edu/About-Department/Faculty120/Charles-Nemeroff.aspx">website</a>. Seems like <a href="http://www.cjr.org/the_observatory/reprimanded_psychiatrist_bad_a.php">something</a> must have happened in 2006 to slow down Chuck's momentum... <div><br /></div><div>What? This is old news? Yeah, I know. But I just hadn't written much about our friends in the world of drug sales/"academics" lately, so I just had to do this.<br /><div><br /></div><div><span class="Apple-style-span" style=" -webkit-border-horizontal-spacing: 2px; -webkit-border-vertical-spacing: 2px; font-family:Arial, Helvetica, sans-serif;font-size:12px;"><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; line-height: 22px; font-size:13px;"><span style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; text-decoration: underline; font-weight: bold; ">Pharmaceutical and Clinical Research Company Scientific Advisory Boards</span></p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Abbott Laboratories<br />- Consultant, Abbott Laboratories, Diagnostics Division, 1986-1992.<br />- Research and Education Advisory Board for Psychiatry<br /> - Member, 1990 - 2006<br /> - Executive Board, 1991 - 1993, 2003 - 2006<br /> -Antidepressant Advisory Board, 1991 - 1992</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">ACADIA Pharmaceuticals Clinical Advisory Board<br /> - Member, 2000 - 2006.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">AstraZeneca Pharmaceuticals<br /> - Psychiatry Advisory Board, 1997 - 2001.<br /> - Chairman, 1999 - 2002.<br /> - Neuroscience Scientific Advisory Board, 1999 - present.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Bristol-Myers-Squibb<br /> - Antipsychotic Advisory Board, 2003 - 2006.<br /> - Antidepressant Advisory Board, 2003 - 2006.<br /> - EMSAM Advisory Board - Chairman, 2005-2006.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Cephalon Pharmaceuticals<br /> - Scientific Advisory Board, 2002</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Comprehensive Neuroscience, Inc.<br /> - Scientific Advisory Board, 1999 - 2004.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Corcept<br /> - Scientific Advisory Board, 2001 - 2006</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Cyberonics<br /> - Scientific Advisory Board, 2002 - 2006.<br /> - Chair, Mechanism of Action Board, 2003 - 2006.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Cypress Biosciences, Inc.<br /> - Board of Directors, 2001 - 2004<br /> - Consultant, 2004 - 2006</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Eli Lilly and Company<br /> - Psychiatry Advisory Board, 1990 - 2000.<br /> - Bipolar Advisory Board, 1998 - 1999.<br /> - Consultant, 2002 - 2003.<br /> - Global Neuroscience Advisory Board, 2005 - 2006.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Forest Laboratories<br /> - Citalopram Clinical Advisory Board, 1997 - 2002.<br /> - Psychiatry Scientific Advisory Board, Chairman, 1999 – 2008.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">GlaxoSmithKline Advisory Board of Psychiatrists<br /> - Chairman, 1991 - 2004.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Janssen Pharmaceuticals<br /> - Mood Disorders Advisory Board, Member and Chairman, 1998 - 2004.<br /> - Topiramate Advisory Board, Member and Chairman, 1999 - 2001.<br /> - Antipsychotic Advisory Board, Member, 1999 - present.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Johnson &amp; Johnson Scientific Advisory Board, 2007- present.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Lundbeck<br /> - Consultant, 2006</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Merck Sharp &amp; Dohme Research Laboratories<br /> - Consultant, Neuroscience Research Center, 1994.<br /> - Mood Disorders Advisory Board, 1999 - 2003.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Merck-MedCo Mental Health Advisory Board<br /> - Member, 1996 – 1998</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Mt. Cook Pharma<br /> - Board of Directors, 2007 - Present</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Neurocrine Biosciences<br /> - Scientific Advisory Board, 1994 - 2004.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Neuronetics<br /> - Scientific Advisory Board, 2006</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Novadel Pharma<br /> - Board of Directors, 2003 - present<br /> - Chair, Scientific Advisory Committee<br /> - Member, Compensation Committee<br /> - Member, Nominating Committee</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Novartis Pharmaceutical Company<br /> - Bipolar Advisory Board Chairman, 2001 - 2003.<br /> - Pediatric Bipolar Advisory Board, 2002 - 2003.<br /> - Antidepressant Advisory Board, 2006.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Organon Pharmaceuticals Psychiatry Advisory Board<br /> - Member, 1997 - 2004.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Otsuka Psychiatry Advisory Board<br /> - Chairman, 2003 - 2006.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">PharmaNeuroboost<br /> - Scientific Advisory Board, 2006 – present.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Pfizer Pharmaceuticals<br /> - Clinical Neuroscience Advisory Board, 2004 - 2006.<br /> - Chair, Antipsychotic Advisory Board, 2004 - 2006.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Quintiles Scientific Advisory Board, 2004 - present</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Revaax<br /> - Stockholder</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Roche Laboratories, a Division of Hoffman-LaRoche, Inc.<br /> - Mania Advisory Board, 1993.<br /> - Pharmocogenomics Advisory Board, 2006</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Sanofi/Synthelabo<br /> - Psychiatry Advisory Board, 2002 - 2005.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">SciRex<br /> - Scientific Advisory Board, 1999 - 2003.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Solvay Pharmaceuticals Psychiatry Advisory Board<br /> - Member, 1991 - 1999.<br /> - Chairman, 1991 - 1999.<br /> - Antipsychotic Advisory Board, 2005 - 2006.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Somerset Pharmaceuticals Psychiatry Advisory Board<br /> - Chair, 2000 - 2004.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Vela Pharmaceuticals<br /> - Scientific Advisory Board, 2001 - 2002.</p><p style="margin-top: 0px; margin-right: 0px; margin-bottom: 8px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; font-size: 13px; line-height: 22px; ">Wyeth-Ayerst Psychiatric Advisory Board<br /> - Chairman and Member, 1995 - 2002.</p></span></div></div>http://clinpsyc.blogspot.com/2010/04/charles-nemeroff-consultant.htmlnoreply@blogger.com (CL Psych)10tag:blogger.com,1999:blog-33960805.post-8420496387558984964Tue, 16 Mar 2010 13:52:00 +00002010-03-16T06:56:07.054-07:00Research Blogging Awards 2010<span style="float: left; padding: 10px;"><a href="http://researchblogging.org/static/index/page/awards"><img alt="Research Blogging Awards 2010" src="http://researchblogging.org/public/static/img/rb_awardlogo_large.gif" style="border:0;"/></a></span><br /><br />Holy cow, I've been nominated for an award?!? Under the category of best health blog, with eight other nominees. Voting is already closed, and I can pretty much guarantee I didn't win, but it's an honor to have been nominated.http://clinpsyc.blogspot.com/2010/03/research-blogging-awards.htmlnoreply@blogger.com (CL Psych)6tag:blogger.com,1999:blog-33960805.post-1676431494753773725Tue, 16 Mar 2010 13:42:00 +00002010-03-16T06:43:34.620-07:00Abilifyghostwritingjournalsmedical educationEditorial Support, CME, and the Primary Care Companion<b></b><br /><img id="m8b9" src="http://docs.google.com/File?id=ddzsmvfh_411dhmzq3dg_b" style="float: left; margin-left: 0pt; margin-right: 1em;" width="325" height="242" />By now, everyone who has been paying attention should know that a journal article which lists "editorial support" is an article that was ghostwritten. Yet the average reader of these articles is apparently uninformed enough to not care. Why else would so many articles get published which feature "editorial support provided by [insert name of ghostwriter here]." One my my favorite journals, under the "so bad, it's good" category, is the Primary Care Companion to the Journal of Clinical Psychiatry. Good articles certainly make their way into the journal, perhaps by accident, but the journal can always be counted on to provide a steady supply of utter garbage.<br /><br />Here's the acknowledgements section from <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781037/" id="e-xp" title="one recent piece">one recent piece</a> in the journal: "Editorial support was provided by George Rogan, MSc, Phase Five Communications Inc, New York, New York. Mr. Rogan reports no other financial affiliations relevant to the subject of this article." And in case you're wondering, "Funding for editorial support was provided by Bristol-Myers Squibb." If you've somehow guessed that this is an advertorial for Abilify, you win. Other ghostwritten pieces of fluff paid for by BMS include <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805571/pdf/pcc11344.pdf" id="wgld" title="an article">an article</a> discussing the safety profile of Abilify in depression. It states that "In conclusion, this post hoc analysis extends previous findings demonstrating that aripiprazole is safe and generally well tolerated as an augmentation strategy to standard ADT in patients with MDD with a history of an inadequate response to antidepressant medication." But Abilify caused akathisia in a quarter of patients - I think <a href="http://clinpsyc.blogspot.com/2009/05/if-youve-been-reading-about-abilify-for.html" id="gv9j" title="that's a problem">that's a problem</a>.<br /><br />But wait... there's more. <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781033/pdf/pcc11215.pdf" id="jz-l" title="An article">An article</a> based on data from two trials, which showed (allegedly) that Seroquel improves anxiety in patients with bipolar disorder. This piece also acknowledges that it was ghostwritten. And we know that AstraZeneca, manufacturer of Seroquel, has <a href="http://clinpsyc.blogspot.com/2009/03/internal-documents-suggest-that.html" id="e:dt" title="cooked the books">cooked the books</a> on Seroquel in the past. Feel free to look through the journal every month and have a giggle at some of the ridiculous pieces that make their way into print. <br /><br /><b>CME<br /><br /></b>You can get your continuing medical education (CME) from the Primary Care Companion as well. One particularly awesome piece of <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736033/pdf/pcc11155.pdf" id="zm_l" title="medical wisdom">medical wisdom</a> <strike>pimped Abilify</strike> educated physicians about the best ways to manage resistant depression. This one is a beauty. It was supported by cash from BMS, which features prominently in the "treat aggressively" message of the piece. The article features none other than Michael Thase as the leading discussant. The same guy who was the leading author on a paper which allegedly showed the wonders of Abilify for depression - despite the pesky fact that patients said <a href="http://clinpsyc.blogspot.com/2009/03/abilify-depression-and-memory-hole.html" id="w42q" title="it didn't work">it didn't work</a>. <br /><br />Back to the CME.. Thase starts off by stating that only a third of patients achieve remission of depressive symptoms during treatment. Given that Abilify is being marketed for treatment-resistant depression, this is a perfect way to start off this <strike>infomercial</strike> educational piece. He adds that failure to achieve remission increases the risk of suicide and puts people at risk for more depression, worse psychiatric outcomes, and all sorts of other bad things. So we better get rid of <i>all symptoms </i>of depression. Thase suggests that clinicians should closely monitor patients to see if their symptoms are remitting. <br /><br />In particular, "Relying on the global statement “I’m definitely better” from the patient overlooks persistent, minor, or residual symptoms. Dr Thase recommended using a standardized symptom assessment measure and keeping track of the patient’s levels of symptom burden." So even if the patient says he or she is much better, don't believe it. Have the patient fill out rating scales and if <i>any symptoms at any level</i> are present, keep treating. In Thase's words, "If the current treatment is well tolerated and the individual has made significant symptom improvement but is still experiencing residual symptoms, then it may be necessary to adjust the treatment dose, add another medication, or combine pharmacotherapy and psychotherapy." Note that adding psychotherapy comes <i>after</i> adding another medication.<br /><br />Then a series of other objective, expert psychiatrists chime in. Dr. Gaynes offers his wisdom, which includes "Dr Gaynes concluded that incomplete remission requires <span style="color:#ff9900;">aggressive</span> identification and management." Don't be afraid - be aggressive. The unspoken message: Hey, using an antipsychotic like Abilify for depression may seem freakin' crazy. But don't worry, you need to be <i>aggressive</i>. Dr. Trivedi then comments about using rating scales to measure side effects. I don't have much to say about his section, but things get worse momentarily...<br /><br />Dr. Papakostas then checks in. "A meta-analysis of randomized, double-blind, placebo controlled studies found that augmentation of various antidepressants with the atypical antipsychotic agents olanzapine, risperidone, and quetiapine was more efficacious than adjunctive placebo therapy. In addition, Dr Papakostas noted that the atypical antipsychotic aripiprazole was recently approved by the US Food and Drug Administration (FDA) for use as an adjunctive therapy to antidepressants in MDD. <span style="color:#ff9900;">Augmenting with atypical antipsychotics has so far been the best studied strategy for managing treatment-resistant depression,</span> said Dr Papakostas." Dr. P was the coauthor of a meta-analysis that provided "considerable evidence" regarding the wonders of antipsychotic therapy for depression. The only problem was that the analysis actually did not find convincing evidence that the drugs were particularly effective, which I discussed in <a href="http://clinpsyc.blogspot.com/2009/12/atypical-antipsychotics-for-depression.html" id="a8my" title="December 2009">December 2009</a>.<br /><br />Next comes Dr. Shelton. Time to be aggressive, again: "Thus, said Dr Shelton, the long-term management of depression should be viewed in the context of acute treatment and the need for <span style="color:#ff9900;">early aggressive management</span> to get the patient as well as possible." Be aggressive by adding Abilify to the antidepressant regimen. If not, your patient won't achieve full remission and will suffer needlessly... "Dr Shelton advised clinicians to <span style="color:#ff9900;">be aggressive</span> in treatment and stay active over time, asking themselves if everything has<br />honestly been done to help the patient." Psychotherapy is given a brief mention in this section, but let's face it -- most physicians think of "be aggressive" as upping the dosage and/or adding medications - not as "let's be aggressive by adding psychotherapy."<br /><br />Then there's the exam at the end. Write up your answers, mail them in, and get your medical education credit. Here's one of the questions...<br />3. Scores on both patient- and clinician-rated scales found that Ms B is still experiencing residual depressive symptoms. You optimize her current SSRI dose, which produces some improvement. She has not reported any problems with side effects. What course of action to improve her outcome has the most comprehensive efficacy data?<br />a. Increase the dose of her current SSRI again<br />b. Augment her current SSRI with another SSRI<br />c. Switch her to a serotonin-norepinephrine reuptake inhibitor<br />d. Augment her current SSRI with an atypical antipsychotic<br /><br />If you guessed that D is the correct answer, you're one step closer to CME credit. And one step closer to writing a prescription for Abilify despite the fact that it is as likely to <a href="http://clinpsyc.blogspot.com/2009/04/abilify-marketing-blitz-atypical.html" id="wmxc" title="induce akathisia">induce akathisia</a> as to induce remission of depressive symptoms. Or that its advantage over placebo is small on several measures and <a href="http://clinpsyc.blogspot.com/2009/06/abilify-for-depression-patients-give-it.html" id="j4i6" title="nonexistent">nonexistent</a> on a patient-rated measure of depression. But D is still the "correct" answer.<br /><br /><span style="float: left; padding: 5px;"><a href="http://www.researchblogging.org"><img alt="ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png" style="border:0;" /></a></span><br /><br />The offending educational piece is cited below:<br /><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=The+Primary+Care+Companion+to+The+Journal+of+Clinical+Psychiatry&amp;rft_id=info%3Adoi%2F10.4088%2FPCC.8133ah3c&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Tackling+Partial+Response+to+Depression+Treatment&amp;rft.issn=1523-5998&amp;rft.date=2009&amp;rft.volume=11&amp;rft.issue=4&amp;rft.spage=155&amp;rft.epage=162&amp;rft.artnum=http%3A%2F%2Farticle.psychiatrist.com%2F%3FContentType%3DSTART%26ID%3D10006169&amp;rft.au=Thase%2C+M.&amp;rft.au=Gaynes%2C+B.&amp;rft.au=Papakostas%2C+G.&amp;rft.au=Shelton%2C+R.&amp;rft.au=Trivedi%2C+M.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Health%2CPsychiatry">Thase, M., Gaynes, B., Papakostas, G., Shelton, R., &amp; Trivedi, M. (2009). Tackling Partial Response to Depression Treatment <span style="font-style: italic;">The Primary Care Companion to The Journal of Clinical Psychiatry, 11</span> (4), 155-162 DOI: <a rev="review" href="http://dx.doi.org/10.4088/PCC.8133ah3c">10.4088/PCC.8133ah3c</a></span>http://clinpsyc.blogspot.com/2010/03/editorial-support-cme-and-primary-care.htmlnoreply@blogger.com (CL Psych)6tag:blogger.com,1999:blog-33960805.post-2087074983016428977Wed, 03 Mar 2010 17:52:00 +00002010-03-03T10:02:34.723-08:00Procter and GambleIf You Don't Learn Your Lesson the First TimeI'm short on time, so I apologize for the lack of details. The short of it: A researcher at the University of Sheffield (Guirong Jang) submitted research findings regarding Procter &amp; Gamble's osteoporosis medication Actonel. However, Sheffield had a contract with P &amp; G to only release Actonel data with the permission of P &amp; G. So Dr. Jang is in BIG trouble - as Sheffield wouldn't want to offend its corporate sponsor by releasing any potentially unflattering data. More can be found <a href="http://www.timeshighereducation.co.uk/story.asp?sectioncode=26&amp;storycode=410419&amp;c=2">here</a>.<br /><br />P &amp; G, Actonel, and trying to effectively manage data to best suit the needs of Actonel's marketing. Hey, wait, this sounds familiar. You may recall the case of Aubrey Blumsohn - a researcher at the same university investigating the same drug, followed by all sorts of strange happenings. Read more on the Blumsohn story <a href="http://www.slate.com/id/2133061/">here</a>.http://clinpsyc.blogspot.com/2010/03/if-you-dont-learn-your-lesson-first.htmlnoreply@blogger.com (CL Psych)0tag:blogger.com,1999:blog-33960805.post-7469999337295800838Wed, 10 Feb 2010 14:00:00 +00002010-02-10T06:01:05.439-08:00child bipolardsm-vT-DDDSay Hello to Temper Dysregulation Disorder with DysphoriaThe buzz around the new version of the DSM is already starting. The draft version is now online and it features a new condition with the ungainly moniker of "Temper Dysregulation Disorder with Dysphoria." That's a friggin' mouthful, so let's try T-Triple D for short. WTF is this disorder? Well, according to my first look, it closely resembles the bad-behavin' kids who have been labeled as bipolar for the last few years. The symptoms are below, and can also be found on the official <a title="DSM-V website" href="http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=397" id="r5fp">DSM-V website</a>:<br /><br /><p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">A. The disorder is characterized by severe recurrent <i>temper outbursts</i> in response to common stressors. </span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.5in; font-family: Georgia;"><span style="font-size:100%;"><span style="color:#000000;">1. The temper outbursts are manifest verbally and/or behaviorally, such as in the form of verbal rages, or physical aggression towards people or property. </span></span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.5in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">2. The reaction is grossly out of proportion in intensity or duration to the situation or provocation. </span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.5in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">3. The responses are inconsistent with developmental level.</span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">B. <i>Frequency</i>: The temper outbursts occur, on average, three or more times per week.</span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;"><span style="color:#000000;">C. <i>Mood between temper outbursts: </i></span></span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.5in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">1. Nearly every day, the mood between temper outbursts is persistently negative (irritable, angry, and/or sad).</span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.5in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">2. The negative mood is observable by others (e.g., parents, teachers, peers). </span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">D. <i>Duration</i>: Criteria A-C have been present for at least 12 months. Throughout that time, the person has never been without the symptoms of Criteria A-C for more than 3 months at a time. </span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;"><span style="color:#000000;">E. The temper outbursts and/or negative mood are present in at least two settings (at home, at school, or with peers) and must be severe in at least in one setting. </span></span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">F. Chronological age is at least 6 years (or equivalent developmental level).</span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">G. The onset is before age 10 years.</span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">H. In the past year, there has never been a distinct period lasting more than one day during which abnormally elevated or expansive mood was present most of the day for most days, and the abnormally elevated or expansive mood was accompanied by the onset, or worsening, of three of the “B” criteria of mania (i.e., grandiosity or inflated self esteem, decreased need for sleep, pressured speech, flight of ideas, distractibility, increase in goal directed activity, or excessive involvement in activities with a high potential for painful consequences; see pp. XX). Abnormally elevated mood should be differentiated from developmentally appropriate mood elevation, such as occurs in the context of a highly positive event or its anticipation. </span></p> <p class="MsoNormal" style="margin: 3pt 0in 0pt 0.2in; font-family: Georgia;"><span style="font-size:100%;color:#000000;">I. The behaviors do not occur exclusively during the course of a Psychotic or Mood Disorder (e.g., Major Depressive Disorder, Dysthymic Disorder, Bipolar Disorder) and are not better accounted for by another mental disorder (e.g., Pervasive Developmental Disorder, post-traumatic stress disorder, separation anxiety disorder). (Note: This diagnosis can co-exist with Oppositional Defiant Disorder, ADHD, Conduct Disorder, and Substance Use Disorders.) The symptoms are not due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.</span></p><br />I've not given this a lot of thought yet. The committee that examined the topic has some discussion of T-Triple D/bipolar <a title="here" href="http://www.dsm5.org/Proposed%20Revision%20Attachments/APA%20Developmental%20Approaches%20to%20Bipolar%20Disorder.pdf" id="t9ct">here</a> and <a title="here" href="http://www.dsm5.org/Proposed%20Revision%20Attachments/Justification%20for%20Temper%20Dysregulation%20Disorder%20with%20Dysphoria.pdf" id="zyvy">here</a>. The committee takes a couple of digs at the the child bipolar diagnosis. So if this new disorder is adopted, we're going to have yet another name for children who behave badly. Fortunately, the criteria appear to require much worse behavior than what has been <a title="passing for &quot;bipolar&quot;" href="http://clinpsyc.blogspot.com/2007/03/bipolar-in-kids-diagnosis-extension.html" id="fp3e">passing for "bipolar"</a> according to some child psychiatrists. The diagnostic threshold is higher and should theoretically lead to fewer kids being unnecessarily diagnosed. But even if the current criteria are adopted without any changes - look for a movement to diagnose "subthreshold" cases of T-DDD, as untreated subthreshold T-DDD will be found to cause untold psychological and physical damages across the world. Damages that can only be mitigated through aggressive treatment using [insert name of latest patented tranquilizer here]. So whatever antipsychotics or "mood stabilizers" are hot in 2013 when the DSM-V is released... they will be the "cure" for T-DDD or bipolar or whatever the hell we decide to label kids with behavior problems.<br /><br />That's my first impression. This is definitely going to be a hot-button topic. There is apparently some mechanism to send comments to the DSM-V folks, since this is only a draft version - feel free to comment here or send your ideas to the DSM-V posse.http://clinpsyc.blogspot.com/2010/02/say-hello-to-temper-dysregulation.htmlnoreply@blogger.com (CL Psych)20tag:blogger.com,1999:blog-33960805.post-3972652094883832615Tue, 05 Jan 2010 23:08:00 +00002010-01-05T15:08:58.487-08:00antidepressantsDo You Have Mild, Moderate, or Severe Depression? Here, Take This Placebo, er, Antidepressant<span style="font-family: georgia;">Yet another meta-analysis with the same damn result -- antidepressants for most cases of depression are placebos. This is in a paper with authors including Jay Amsterdam, Richard Shelton, and Jan Fawcett, who are not exactly cut from the Peter Breggin mold. This was based on six studies which compared antidepressant to placebo in patients who had a wide range of depression severity. Key results:</span><br /><ul style="font-family: georgia;"><li>Mild to moderate depression: Effect size of d = .11, which is tiny (and was not statistically significant)<br /></li><li>Severe depression: Effect size of d = .17, which is pretty darn small (and not statistically significant)</li><li>Very severe depression: Effect size of d = .47, which is moderate.</li></ul><br /><span style="font-family: georgia;">Hmmmm. Not looking so hot. Of course, anyone who has paid attention to the clinical trial literature on antidepressants over the past 10 years or so already knew this. But now it's in JAMA, so a wider audience may now pay attention. Or ignore it. Good marketing usually beats science, so maybe this won't make any difference.</span><br /><br /><span style="font-family: georgia;">Antidepressants for all but very severe depression: All the benefits of placebo </span><i style="font-family: georgia;">plus</i><span style="font-family: georgia;"> the added bonus of side effects. Sign me up! To quote the authors: </span><span style="font-family: georgia;font-size:100%;" >"</span><span style="font-family: georgia;font-family:verdana, arial, helvetica, sans-serif;font-size:100%;" >What makes our findings surprising is the high level of depression symptom severity that appears to be required for clinically meaningful drug/placebo differences to emerge, particularly given the evidence that the majority of patients receiving ADM in clinical practice present with scores below these levels.</span><span style="font-family: georgia;">" In other words, most people who receive antidepressants would likely have done just as well on placebo (without the side effects). </span><br /> <br /><span style="font-family: georgia;"> A few other posts on the topic:</span><br /> <ul style="font-family: georgia;"><li>The <a title="long-lasting" target="_blank" href="http://clinpsyc.blogspot.com/2008/09/that-pesky-long-lasting-placebo.html" id="ba7w">long-lasting</a> placebo effect</li><li><a title="Sexual side effects" target="_blank" href="http://clinpsyc.blogspot.com/2008/05/sexual-side-effects-of-ssris-is.html" id="sr1x">Sexual side effects</a> of SSRIs</li><li>Paxil:<a title="How to lie" target="_blank" href="http://clinpsyc.blogspot.com/2008/04/paxil-lies-and-lying-researchers-who.html" id="e01n"> How to lie</a></li><li>The much-vaunted <a title="public health" target="_blank" href="http://clinpsyc.blogspot.com/2008/03/nemeroff-confirms-kirsch-ssris-offer.html" id="lq-o">public health</a> benefits of antidepressants</li><li>Antidepressants offer <a title="weak efficacy" target="_blank" href="http://clinpsyc.blogspot.com/2008/02/antidepressants-meet-new-news-same-as.html" id="peok">weak efficacy</a> for all but most severe depression</li><li>Hiding <a title="negative data" target="_blank" href="http://clinpsyc.blogspot.com/2008/01/antidepressants-hiding-and-spinning.html" id="q8lj">negative data</a> on antidepressants</li><li>Suicidal tendencies? Nah, not <a title="here" target="_blank" href="http://clinpsyc.blogspot.com/2007/12/blast-from-past-suicide-data-regarding.html" id="pdq4">here</a><br /> </li></ul> <span style="font-family: georgia;">I've linked the </span><a style="font-family: georgia;" title="abstract" target="_blank" href="http://jama.ama-assn.org/cgi/content/short/303/1/47?home" id="b7:g">abstract</a><span style="font-family: georgia;"> of the latest JAMA study here. Enjoy.</span>http://clinpsyc.blogspot.com/2010/01/do-you-have-mild-moderate-or-severe.htmlnoreply@blogger.com (CL Psych)22tag:blogger.com,1999:blog-33960805.post-4418469019536571863Wed, 16 Dec 2009 20:46:00 +00002009-12-16T13:08:56.519-08:00AbilifyantidepressantsantipsychoticdepressionEvidenceAtypical Antipsychotics For Depression: Now With "Considerable Evidence"<span style="padding: 5px; float: left;"><a href="http://www.researchblogging.org/"><img alt="ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png" style="border: 0pt none ;" /></a></span><br />I've been wanting to write about this for months. Here goes. We know that antipsychotics are the new panacea for all things mental health-related, including depression (<a title="1" target="_blank" href="http://clinpsyc.blogspot.com/2009/07/thanks-for-your-service-now-take-this.html" id="h9x.">1</a>, <a title="2" target="_blank" href="http://www.furiousseasons.com/archives/2009/04/10_percent_of_depressed_patients_now_take_antipsychotics_1.html" id="w9ih">2</a>, <a title="3" target="_blank" href="http://clinpsyc.blogspot.com/2009/04/abilify-marketing-blitz-atypical.html" id="cg7j">3</a>). But critics kept pointing to a pesky lack of evidence that such treatments actually worked. Bristol-Myers Squibb, manufacturer of Abilify, has been running a disinformation campaign in medical journals to tout its drug as an antidepressant. Their attempts to paint a positive picture of Abilify's antidepressant properties and its allegedly fantastic safety/tolerability profile have been simultaneously tragic and amusing (<a title="1" target="_blank" href="http://clinpsyc.blogspot.com/2009/06/abilify-for-depression-patients-give-it.html" id="ru84">1</a>, <a title="2" target="_blank" href="http://clinpsyc.blogspot.com/2009/03/abilify-depression-and-memory-hole.html" id="t-v4">2</a>, <a title="3" target="_blank" href="http://clinpsyc.blogspot.com/2009/01/abilify-for-depression-im-not-only.html" id="bgmv">3</a>).<br /><br />We're now moving on to something bigger... It ain't just Abilify, folks. It's <i>all </i>the atypicals. They are <i>all </i>antidepressants. According to the authors of a recent meta-analysis, for atypical antipsychotics: "At present, this body of evidence is considerably larger than that for any other augmentation strategy in the treatment of major depressive disorder." In other words, if you are not prescribing atypicals for your patients who don't show adequate response to antidepressants, you are not practicing evidence-based medicine. You are a [bleeping] cowboy who is willfully disregarding science. You are denying your patients the best possible treatment. The authors don't actually say any of those things, but those are the implications. If the evidence for using antipsychotics is "considerably larger" than the evidence for anything else, then the implications are clear-cut. And this is exactly how this study will be cited. Salespeople, from drug reps to academic psychiatrists, to practitioners looking to earn a few thousand extra bucks on the side through pharma speaking gigs, will discuss this study as if it were a landmark finding.<br /><br /><b>Response and Remission: </b>But the "evidence" is not all that convincing. Here's why... The authors pooled together the results of 16 randomized controlled trials. In these studies, patients had failed to respond adequately (using various definitions) to an antidepressant. Patients were then assigned to receive either an atypical antipsychotic or a placebo in addition to their antidepressant. Outcomes were then tabulated somewhere between 4 and 12 weeks later. The results seem clear cut -- if your brain is turned to "off" -- the response rates for atypicals was 44% compared to 30% for placebo. The remission rates were 31% for atypicals and 17% for placebo. The advantage for atypicals is statistically significant. Well, there you have it. Done deal. Ask your doctor about Abilify/Zyprexa/Seroquel today...<br /><br />But the most important thing in a treatment outcome study is... the outcomes. The authors of the meta-analysis did not bother to actually measure change in scores on rating scales. Instead, they only used response and remission rates. There is absolutely no good reason for doing this. It's potentially quite misleading. Doctors like remission and response rates because they provide the illusion that we are measuring depression exactly. A "responder" got a lot better and is functioning reasonably well whereas a "non-responder" is in bed 12 hours a day while spending the rest of her time watching the E! Network, eating Bon-Bons, and sobbing constantly. But it's not nearly that scientific. A "responder" is usually defined as someone who got 50% better on his or her depression rating score during the study period. So Bob's depression rating score improved by 52% (he's a responder), but Amy's score only improved by 48%, so she's a nonresponder. Is this 4% difference really meaningful?<br /><br />Let's look at the following dataset for 20 participants in a fictional study...<br /><br />Improvements in depression over course of 10 week study<br /><div style=""><table style="width: 193px; height: 288px;" class="" id="a7jk" bgcolor="#f6b26b" border="1" bordercolor="#000000" cellpadding="3" cellspacing="0"><tbody><tr><td width="50%"><b>Drug<br /></b></td><td width="50%"><b>Placebo<br /></b></td></tr><tr><td width="50%">40%<br /></td><td width="50%">30%<br /></td></tr><tr><td width="50%">55%<br /></td><td width="50%">60%<br /></td></tr><tr><td width="50%">50%<br /></td><td width="50%">45%<br /></td></tr><tr><td width="50%">55%<br /></td><td width="50%">48%<br /></td></tr><tr><td width="50%">52%<br /></td><td width="50%">48%<br /></td></tr><tr><td width="50%">60%<br /></td><td width="50%">55%<br /></td></tr><tr><td width="50%">60%<br /></td><td width="50%">55%<br /></td></tr><tr><td width="50%">10%<br /></td><td width="50%">25%<br /></td></tr><tr><td width="50%">20%<br /></td><td width="50%">10%<br /></td></tr><tr><td width="50%">25%<br /></td><td width="50%">30%<br /></td></tr></tbody></table></div><br />Using a 50% improvement to determine if a patient is a "responder", we get a 60% response rate on drug and a 30% response rate on placebo. Lazy logic says: Oooh -- the drug is twice as effective as placebo. But is we take the average for each group, we get an average improvement of 42.7% on the drug compared to 40.6% on placebo. See the problem with response and remission rates? Similar arguments have been made by <a title="smarter people" target="_blank" href="http://www.bmj.com/cgi/content/full/331/7509/155" id="b.vr">smarter people</a> than myself.<br /><br />Putting outcomes into convenient little categories makes good sense when the categories themselves make sense - events like having a heart attack, getting pregnant, or dying. If the death rate on a drug is 4% compared to 2% on a placebo, then the drug really reduced death by 50%. But if the "remission rate" or "response rate" for depression is 40% on drug compared to 20% on placebo, that does <i>not </i>mean the drug is twice as effective as placebo in treating depression. If you need to score a 7 or below on a depression rating scale to be "in remission", but you score an 8, are you <i>really</i> much worse off than the person who scored a 7?<br /><br />Am I saying that the drugs really just squeaked by placebo in these studies? Well, I've read the Abilify studies and posted on them previously - in those studies, Abilify barely beat the placebo. And in the opinion of the patients themselves, Abilify <a title="didn't beat placebo" target="_blank" href="http://clinpsyc.blogspot.com/2009/06/abilify-for-depression-patients-give-it.html" id="djfp">didn't beat placebo</a> at all. And the studies were designed to benefit Abilify, not to actually see if the drug worked. As I noted <a title="previously" target="_blank" href="http://clinpsyc.blogspot.com/2007/07/abilify-its-tricky-to-rock-fda.html" id="lg8y">previously</a>...<br /><blockquote>Patients were initially assigned to receive an antidepressant plus a placebo for eight weeks. Those who failed to respond to treatment were assigned to Abilify + antidepressant or placebo + antidepressant. Those who responded during the initial 8 weeks were then eliminated from the study. <span style="color: rgb(255, 0, 0);">So we've already established that antidepressant + placebo didn't work for these people -- yet they were then assigned to treatment for 6 weeks with the same treatment (!) and compared to those who were assigned antidepressant + Abilify. So the antidepressant + placebo group started at a huge disadvantage because it was already established that they did not respond well to such a treatment regimen. <span style="color: rgb(0, 0, 0);">No wonder Abilify came out on top (albeit by a modest margin).</span></span><br /><br /><span style="color: rgb(255, 0, 0);"><span style="color: rgb(0, 0, 0);">Here's an analogy. A group of 100 students is assigned to be tutored by Tutor A regarding math. The students are all tutored for 8 weeks. The 50 students whose math skills improve are sent on their merry way. That leaves 50 students who did not improve under Tutor A's tutelage. So Tutor B comes along to tutor 25 of these students, while Tutor A sticks with 25 of them. Tutor B's students do somewhat better than Tutor A's students on a math test 6 weeks later. Is Tutor B better than tutor A? Not really a fair comparison between Tutor A and Tutor B, is it?</span></span><br /></blockquote>I've not read the other antipsychotics for depression studies. I'll even give them the benefit of the doubt and assume they were not designed in the same biased manner as the Abilify trials. It is, however, worth noting that the "benefit" of Abilify, in terms of response and remission rates compared to placebo, was about the same as for the other atypicals. Which leads me to think that the other atypicals probably show similar marginal benefits for depression.<br /><br />But now, based solely on potentially quite misleading response and remission rates, an article appears in the American Journal of Psychiatry - a piece that has the potential to ramp up the prescribing of antipsychotics for depression to an even more ridiculous level. Let the good times roll.<br /><br />Source of ironclad evidence that atypical antipsychotics are antidepressants (until you actually read the paper):<br /><br /><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=American+Journal+of+Psychiatry&amp;rft_id=info%3Adoi%2F10.1176%2Fappi.ajp.2009.09030312&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Atypical+Antipsychotic+Augmentation+in+Major+Depressive+Disorder%3A+A+Meta-Analysis+of+Placebo-Controlled+Randomized+Trials&amp;rft.issn=0002-953X&amp;rft.date=2009&amp;rft.volume=166&amp;rft.issue=9&amp;rft.spage=980&amp;rft.epage=991&amp;rft.artnum=http%3A%2F%2Fajp.psychiatryonline.org%2Fcgi%2Fdoi%2F10.1176%2Fappi.ajp.2009.09030312&amp;rft.au=Nelson%2C+J.&amp;rft.au=Papakostas%2C+G.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Health%2CPsychiatry">Nelson, J., &amp; Papakostas, G. (2009). Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials <span style="font-style: italic;">American Journal of Psychiatry, 166</span> (9), 980-991 DOI: <a rev="review" href="http://dx.doi.org/10.1176/appi.ajp.2009.09030312">10.1176/appi.ajp.2009.09030312</a></span>http://clinpsyc.blogspot.com/2009/12/atypical-antipsychotics-for-depression.htmlnoreply@blogger.com (CL Psych)11tag:blogger.com,1999:blog-33960805.post-6519700149178823177Fri, 30 Oct 2009 13:39:00 +00002009-10-30T06:42:56.341-07:00depressionNeuroneticstranscranial magnetic stimulationTranscranial Magnetic Stimulation for Depression: Not so Effective, but FDA Approved<span style="float: left; padding: 5px;"><a href="http://www.researchblogging.org"><img alt="ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png" style="border:0;" /></a></span><br />Apparently, the FDA will approve just about anything as an antidepressant. Despite patients indicating that <a title="they don't" target="_blank" href="http://clinpsyc.blogspot.com/2009/06/abilify-for-depression-patients-give-it.html" id="nq6b">they don't</a> perceive Abilify to work as an antidepressant, the FDA approved it, likely leading to tens of thousands of Americans being able to enjoy a taste of akathisia while getting all the psychological benefits of a placebo. Good work, FDA. The shift of antipsychotics into antidepressants has been documented in many places and is, ironically, very depressing (<a title="1" target="_blank" href="http://clinpsyc.blogspot.com/2009/04/abilify-marketing-blitz-atypical.html" id="i8uh">1</a>, <a title="2" target="_blank" href="http://www.latimes.com/features/health/la-hew-aboutabilify13-2009apr13,0,3598881.story" id="vaz0">2</a>, <a title="3" target="_blank" href="http://www.latimes.com/features/health/la-he-antipsychotics13-2009apr13,0,2324987.story" id="jmdp">3</a>, <a title="4" target="_blank" href="http://clinpsyc.blogspot.com/2009/03/abilify-depression-and-memory-hole.html" id="hfda">4</a>).<br /><br />The FDA's "anything goes" attitude regarding antidepressants apparently extends to mediocre medical devices. In 2007, a paper in <i>Biological Psychiatry </i>presented results from a large trial comparing TMS to sham TMS. The article concluded that the treatment was a fantastic option for depression. Well, close to that anyway. That actually wrote that "<span style="color: rgb(255, 153, 0);"><span style="color: rgb(255, 0, 0);">Transcranial magnetic stimulation was effective in treating major depression</span> </span>with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder."<br /><br />Before all of us poor depressed souls get in line for some sweet magnetic stimulation, maybe we should, like, look at the evidence. On the primary measure of outcome, the Montgomery-Asberg Depression Rating Scale, the results weren't quite statistically significant. So the sponsor tried to convince the FDA Neurological Devices Panel that the secondary measures showed super-impressive results. The problem: They didn't. The FDA review panel thought a few things (as can be seen in its entirety <a title="here" target="_blank" href="http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/ucm124779.htm" id="zlh1">here</a>):<br /><ul><li>The Panel’s consensus was that the efficacy was not established; some stated that the device’s effectiveness was “small,” “borderline,” “marginal” and “of questionable clinical significance.” The Study 01 endpoint with a p value of 0.057 per se was not considered a fatal flaw in the study analysis. <span style="color: rgb(255, 0, 0);">The Panel did not believe that clinical significance was demonstrated with these results.</span></li><li>In general, the panel believed that the analyses of the secondary effectiveness endpoints did not contribute significant information to help establish the effectiveness of the device.</li><li><span style="color: rgb(255, 0, 0);">The Panel agreed that unblinding was greater in the active group, and considering the magnitude of the effect size, it may have influenced the study results.</span> (35.8% of people receiving TMS reported pain at the application site compared to only 3.8% in the sham TMS group. This is a quick way to make a study unblind, as people experiencing pain could logically surmise that they were receiving TMS).</li><li><span style="color: rgb(255, 0, 0);">The Panel stated that there were too many non-random dropouts to reliably interpret these results.</span> The Panel’s consensus was that the Week 6 data was of limited value and did not provide supportive data for establishing effectiveness. (After week 4, patients who did not show adequate improvement were given the option to quit the double-blind study; over half of patients departed the study after week 4).<br /></li></ul>One more doozy. A quote follows from a letter to the editor in <i>Biological Psychiatry</i> in which TMS is taken to task.<br /><blockquote>The authors note that some patient outcome measures were collected in the trial but omitted from the article. Of the 15 secondary end points the authors included in the paper, 11 were statistically significant. Of 11 secondary end points not included, 2 were statistically significant. <span style="color: rgb(255, 0, 0);">Thus, the published end points were three times more likely to be statistically significant than the unpublished ones.</span><br /></blockquote>TMS was denied FDA-approval in January, 2007. But in October 2008, the FDA had a <a title="change of heart" target="_blank" href="http://www.accessdata.fda.gov/cdrh_docs/pdf6/K061053.pdf" id="j-gg">change of heart</a>, approving the device. I'm not quite sure what changed the mind of the FDA. <br /><br />The following disclaimer on the device's <a title="website" target="_blank" href="http://www.neurostartms.com/Patient/NeuroStar-Effectiveness.aspx" id="xrm0">website</a> is a bit funny:<br /><blockquote>NeuroStar TMS Therapy has not been studied in patients who have not received prior antidepressant treatment. Its effectiveness has also not been established in patients who have failed to receive benefit from two or more prior antidepressant medications at minimal effective dose and duration in the current episode. <br /></blockquote>So it's only demonstrated (weak) efficacy in people who have failed one (not zero, not more than one) antidepressant trial. Impressive, eh? To summarize, the sponsor and its affiliated academics wrote a paper in a major psychiatry journal in which positive outcomes were three times as likely to be reported as negative outcomes. The efficacy data were unimpressive according to an FDA panel -- and these panels are not known for being particularly choosy about efficacy data. It seemed that TMS was dead in the water, only to be resurrected in the form of a surprising FDA approval. And if being resurrected from the grave doesn't make for a great Halloween post, then what does?<br /><br />Offending Study:<br /><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Biological+Psychiatry&amp;rft_id=info%3Adoi%2F10.1016%2Fj.biopsych.2007.01.018&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Efficacy+and+Safety+of+Transcranial+Magnetic+Stimulation+in+the+Acute+Treatment+of+Major+Depression%3A+A+Multisite+Randomized+Controlled+Trial&amp;rft.issn=00063223&amp;rft.date=2007&amp;rft.volume=62&amp;rft.issue=11&amp;rft.spage=1208&amp;rft.epage=1216&amp;rft.artnum=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0006322307001461&amp;rft.au=O%E2%80%99Reardon%2C+J.&amp;rft.au=Solvason%2C+H.&amp;rft.au=Janicak%2C+P.&amp;rft.au=Sampson%2C+S.&amp;rft.au=Isenberg%2C+K.&amp;rft.au=Nahas%2C+Z.&amp;rft.au=McDonald%2C+W.&amp;rft.au=Avery%2C+D.&amp;rft.au=Fitzgerald%2C+P.&amp;rft.au=Loo%2C+C.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Health%2CPsychiatry">O’Reardon, J., Solvason, H., Janicak, P., Sampson, S., Isenberg, K., Nahas, Z., McDonald, W., Avery, D., Fitzgerald, P., &amp; Loo, C. (2007). Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial <span style="font-style: italic;">Biological Psychiatry, 62</span> (11), 1208-1216 DOI: <a rev="review" href="http://dx.doi.org/10.1016/j.biopsych.2007.01.018">10.1016/j.biopsych.2007.01.018</a></span><br /><br />Letter to Editor:<br /><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=Biological+Psychiatry&amp;rft_id=info%3Adoi%2F10.1016%2Fj.biopsych.2009.03.026&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Transcranial+Magnetic+Stimulation+Not+Proven+Effective&amp;rft.issn=00063223&amp;rft.date=2009&amp;rft.volume=&amp;rft.issue=&amp;rft.spage=&amp;rft.epage=&amp;rft.artnum=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0006322309009664&amp;rft.au=Yu%2C+E.&amp;rft.au=Lurie%2C+P.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Health%2CPsychiatry">Yu, E., &amp; Lurie, P. (2009). Transcranial Magnetic Stimulation Not Proven Effective <span style="font-style: italic;">Biological Psychiatry</span> DOI: <a rev="review" href="http://dx.doi.org/10.1016/j.biopsych.2009.03.026">10.1016/j.biopsych.2009.03.026</a></span>http://clinpsyc.blogspot.com/2009/10/transcranial-magnetic-stimulation-for.htmlnoreply@blogger.com (CL Psych)15tag:blogger.com,1999:blog-33960805.post-8180896682423385040Sat, 19 Sep 2009 15:28:00 +00002009-09-22T06:55:51.738-07:00ghostwritingkey opinion leadersciencestealth marketingLend Me Your NameJournalism regarding the horrors of ghostwritten papers in medical journals is all the rage these days (<a title="1" target="_blank" href="http://blogs.wsj.com/health/2009/09/18/medical-journal-ghostwriting-time-to-do-something/" id="kglu">1</a>, <a title="2" target="_blank" href="http://www.npr.org/blogs/health/2009/09/ghostwriters_busy_writing_for.html" id="bnx1">2</a>, <a title="3" target="_blank" href="http://thestar.blogs.com/ethics/2009/09/the-problem-with-ghostwriting.html" id="c3_-">3</a>). Here's my very small contribution. The document shown below from a medical writing company has been described <a title="elsewhere" target="_blank" href="http://speakingofmedicine.plos.org/2009/08/07/ghostwriting-101/" id="brfw">elsewhere</a>. But it is worth seeing in its glory firsthand. The document is from Wyeth's ghostwriting firm, DesignWrite. It was part of the Premarin/hormone replacement therapy disaster (see below). Perhaps you remember the era when hormone replacement therapy was being prescribed for all sorts of people because it was supposedly a wonder treatment. So what if it <a href="http://www.jsonline.com/features/health/38283649.html">increased risk</a> for breast cancer and perhaps other conditions as well? Not to worry, DesignWrite could get around that...<br /><br />In layman's terms, it goes like this... Wyeth -- you give us some hints about the marketing spin you'd like us to put on your studies. We'll then write up the studies accordingly and have big-name academics sign off as if they had something to do with our oh-so-objective "research". And don't worry, Wyeth, you get to review all papers we write up to make sure we market your drug appropriately.<br /><br /><div id="z23w" style="text-align: left;"><img src="http://docs.google.com/File?id=ddzsmvfh_402hdk2kdcj_b" width="561" height="309" /></div><br />We now know that several academics participated in this program. To quote <a title="one ethicist" target="_blank" href="http://www.cmaj.ca/earlyreleases/9sept09_ghostwriting.shtml" id="j6gl">one ethicist</a>, regarding the academics who lent their names as authors: "They sold their credentials for false credit and money." DesignWrite's current slogan is: "Where we put clinical data to work." Hmmm. DesignWrite gets paid, Wyeth gets paid, and the academics who lend their names get paid and/or get another publication to boost their stock in the academic world.<br /><br />Oh, and patients, what did they get out this... <a title="breast cancer" target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed/18372396?ordinalpos=17&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" id="jaf4">breast cancer</a>. But who cares about them anyway -- patients are just little buckets of money; it's not like they're real human beings.<br /><p>A summary of <a title="the results" target="_blank" href="http://www.whi.org/findings/ht/eplusp_3yr.php" id="l3:k">the results</a> that led to the downfall of hormone replacement therapy<br /></p> <blockquote> <p>Three years after stopping hormone therapy, women who had taken study pills with active estrogen plus progestin no longer had an increased risk of cardiovascular disease (heart disease, stroke, and blood clots) compared with women on placebo. The lower risk of colorectal cancer seen in women who had taken active E+P disappeared after stopping the intervention. The benefit for fractures (broken bones) in women who had taken active E+P also disappeared after stopping hormone therapy. On the other hand, the risk of all cancers combined in women who had used E+P increased after stopping the intervention compared to those on placebo. This was due to increases in a variety of cancers, including lung cancer. After stopping the intervention, mortality from all causes was somewhat higher in women who had taken active E+P pills compared with the placebo.</p> <p><i>Based on the findings mentioned above, the study’s global index that summarized risk and benefits was unchanged, showing that the health risks exceeded the health benefits from the beginning of the study through the end of this three year follow-up. The follow-up after stopping estrogen plus progestin confirms the study’s main conclusion that combination hormone therapy (E+P) should not be used to prevent disease in healthy, postmenopausal women.</i> The most important message to women who have stopped this hormone therapy is to continue seeing their physicians for rigorous prevention and screening activities for all important preventable health conditions.</p> </blockquote> I'm glad to see that ghostwriting is now the topic <i>du jour</i> in health journalism. But in a few weeks, the attention will vanish as the drug industry and its associated writing firms will agree to allegedly stringent guidelines that ensure this never happens again. And nothing will actually change. I mean, seriously, do you think academic researchers are going to write their own papers? Do you think drug companies are going to stop hiring writers to expertly spin the data? The current system works too well for it to simply go away.<br /><br />Thanks to an alert reader for sending this document along. You can <a href="http://dida.library.ucsf.edu/">search</a> for more documents at the Drug Industry Document Archive, including those from Wyeth and DesignWrite. Happy digging!http://clinpsyc.blogspot.com/2009/09/lend-me-your-name.htmlnoreply@blogger.com (CL Psych)1tag:blogger.com,1999:blog-33960805.post-3357421396080824551Wed, 09 Sep 2009 17:00:00 +00002009-09-09T10:26:52.154-07:00antipsychoticasenapineDaniel Carlatkey opinion leadermarketingWanted: Drug Pimp/Key Opinion Leader<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="http://docs.google.com/File?id=ddzsmvfh_400c3ccnsfj_b"><img style="margin: 0pt 10px 10px 0pt; float: left; cursor: pointer; width: 220px; height: 202px;" src="http://docs.google.com/File?id=ddzsmvfh_400c3ccnsfj_b" alt="" border="0" /></a>Daniel Carlat from the Carlat Psychiatry Blog received an invitation to the key opinion leader club from the good people at Schering-Plough. The company wanted him to read their slides to other physicians in order to promote their brand spanikn' new antipsychotic/mood stabilizer Saphris (asenapine). Because, of course, if he reads the slides, they are more credible than if read by one of those sleazy drug reps; it's so much more classy and believable if an "independent" psychiatrist reads the company's marketing copy.<br /><br />Carlat posted the documents used in the attempt to recruit him (<a href="http://www.scribd.com/doc/19542468/ScheringPlough-Cover-Letter">cover letter</a>, <a href="http://www.scribd.com/doc/19542466/Schering-Plough-Agreement">speaker bureau arrangement</a>, <a href="http://www.scribd.com/doc/19542474/ScheringPlough-Speakers-Fees">pimp, er, speaker fees</a>) Everyone should read them. Speakers are only allowed to rake in $170,000 of dirty money through this program. I suppose anything more would make them look like shameless drug pimps. But if you were to take, say, $50k for your "educational" services, that would be totally acceptable, right? I hereby nominate anyone who accepts Schering-Plough's generous offer for the much coveted <a href="http://clinpsyc.blogspot.com/2007/04/paxil-and-pimping.html">Golden Goblet</a> Award.<br /><br />What's the deal with this Saphris drug, anyway? One neuropsychologist reviewed the data and found that it promises to be <a href="http://chekhovsgun.blogspot.com/2009/09/saphris-its-different-without-actually.html">yet another also-ran</a> atypical antipsychotic, at best. Some have also raised questions of whether the drug deserved <a href="http://shearlingsplowed.blogspot.com/2009/09/saphris-its-different-without-actually.html">FDA approval</a> at all. Get ready for some ghostwritten articles that present the evidence surrounding Saphris in a ridiculously biased manner, for <a href="http://clinpsyc.blogspot.com/2009/08/key-opinion-leader-syndrome.html">key opinion leaders</a> to travel to conferences extolling its virtues, and for the rest of the usual marketing tricks.http://clinpsyc.blogspot.com/2009/09/wanted-drug-pimpkey-opinion-leader.htmlnoreply@blogger.com (CL Psych)3tag:blogger.com,1999:blog-33960805.post-5333584188114760343Mon, 31 Aug 2009 12:47:00 +00002009-08-31T05:47:54.101-07:00key opinion leaderKey Opinion Leader SyndromeI ran across a rather hilarious article from <i><a title="Medical Hypotheses" target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed/19201547?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" id="lf-t">Medical Hypotheses</a></i>, in which David Healy described "Krapelin-Fraud Syndrome", which I have also dubbed "Key Opinion Leader Syndrome." See below for the diagnostic criteria.<br /><br /><blockquote><img style="float: left; margin-left: 0pt; margin-right: 1em;" src="http://docs.google.com/File?id=ddzsmvfh_400c3ccnsfj_b" width="224" height="206" />In line with current neo-Kraepelinian thinking, we put forward operational criteria for this new disorder for provisional inclusion in ICD-XI or DSM-V. An affected subject should meet at least 2 of criteria A–D and 2 more from criteria E–J. Fulfillment of all criteria A–D in the absence of any other features of the disorder will make the diagnosis, although this may represent a syndromal variant.<br />(A) A pervasive pattern of travelling to scientific conferences and talking about research data that he has had no involvement in generating.<br />(B) Episodic logosagnosia.<br />(C) Unusual abilities to compartmentalise information.<br />(D) Will have a significant number of ‘‘ghost-written” articles.<br />(E) Actively seeks admiration by peers and subordinates.<br />(F) An exaggerated sense of own talents, which can be inferred from expectations of recognition as an expert in the absence of commensurate achievements. Happy in the role of opinion leader.<br />(G) Has a sense of entitlement, i.e. unreasonable expectations of favorable treatment from symposium and congress organisers.<br />(H) Liable to profound dysphoria if not involved with the ‘‘academic action”.<br />(I) May be unreasonably envious of the scientific achievements of others and is liable to denigrate these. Would also be unhappy if his colleagues had appeared on ‘‘educational” videos and he had not.<br />(J) Is unaware of the disorder quality of the syndrome.<br /></blockquote> Two case studies are included, one of which reads in part:<br /><blockquote>One of the striking features of his lecturing is the dissociation between his reputation as a critical and skeptical lecturer when dealing with topics on the main programme of the meeting and the extent to which he may be prepared to offer apparently enthusiastic and uncritical endorsement for a compound in a satellite symposium. Very frequently this uncritical endorsement will involve the recycling of outdated ideas, which it is difficult to believe that either B or indeed many of his audience can conceivably believe and which indeed he may contradict within the hour at another symposium.<br /></blockquote> Hmmmm. Enthusiastic and uncritical endorsement of [insert product name here]. That reminds me of <a title="a post" target="_blank" href="http://clinpsyc.blogspot.com/2007/12/seroquel-for-everything-and-academic.html" id="fz_o">a post</a> or <a title="two" target="_blank" href="http://clinpsyc.blogspot.com/2008/09/cymbalta-schatz-storm-duplicate.html" id="s5jr">two</a> I've written... I made a rough <a title="list of symptoms" target="_blank" href="http://clinpsyc.blogspot.com/2008/07/fda-gives-thumbs-up-to-kiddie-bipolar.html" id="d2c1">list of symptoms</a> for KOL Syndrome in July 2008. Different symptoms, but same idea.http://clinpsyc.blogspot.com/2009/08/key-opinion-leader-syndrome.htmlnoreply@blogger.com (CL Psych)4tag:blogger.com,1999:blog-33960805.post-7214690129697465250Wed, 29 Jul 2009 16:28:00 +00002009-07-29T09:34:20.654-07:00antipsychoticasenapineThe Asenapine Chronicles?I'm not sure what to make of this. A lot of documents have <a href="http://shearlingsplowed.blogspot.com/2009/07/over-1000-pages-of-saphris-asenapine.html">become available</a> on the Shearlings Got Plowed blog, which deal with the new antipsychotic drug asenapine. If I had the time, I'd be burying myself in the documents, as SGP claims that something fishy is going on. I encourage all interested readers to take a good, long look at the documents to see what (if anything) is happening.<br /><br />Documents such as <a href="http://4.bp.blogspot.com/_M_OtwEgZgAk/Sm_MdmRwQ1I/AAAAAAAADHo/H8_QYAy3Z6w/s1600-h/SGP-Asenapine-FDA-07-28-09-.jpg">this one</a> will catch your interest...http://clinpsyc.blogspot.com/2009/07/asenapine-chronicles.htmlnoreply@blogger.com (CL Psych)1tag:blogger.com,1999:blog-33960805.post-8350489422658913131Tue, 21 Jul 2009 01:11:00 +00002009-07-20T18:11:56.902-07:00antipsychoticThanks For Your Service, Now Take This Pill<img id="bzeo" style="float: left; margin-left: 0pt; margin-right: 1em;" src="http://docs.google.com/File?id=ddzsmvfh_397hwcw23hq_b" width="299" height="189" />According to a freshly published study, one in five depressed patients receiving services through the VA healthcare system in the United States is taking an antipsychotic. Of those taking antipsychotics, 43% were taking them at high doses (schizophrenia doses rather than lower doses typically used in treating depression). The study, published in the <a title="Journal of Clinical Psychiatry" target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed/19422760?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" id="fdc0">Journal of Clinical Psychiatry</a>, excluded patients with schizophrenia or bipolar diagnoses -- this means that the antipsychotics given to the depressed folks weren't mainly used to treat psychosis or mania. The sample size was over 190,000 patients, so one can't fault the study for not including enough patients. The researchers examined drugs taken within one week of their last antipsychotic prescription and found that 24% of patients were taking multiple antipsychotics at that point. <br /><br />The most used medication was Seroquel. This is <a title="not suprising" target="_blank" href="http://www.furiousseasons.com/archives/2007/12/doping_up_the_troops_seroquel_1_high_in_iraq.html" id="sqr4">not suprising</a>. Patients seen in mental health speciality clinics were the most likely to receive antipsychotics. So what are the consequences? Well, let's see. There's the high rate of akathisia and <a title="medicore efficacy" target="_blank" href="http://clinpsyc.blogspot.com/2009/06/abilify-for-depression-patients-give-it.html" id="zzg_">medicore efficacy</a> of <a title="Abilify" target="_blank" href="http://clinpsyc.blogspot.com/2009/05/if-youve-been-reading-about-abilify-for.html" id="cyia">Abilify</a>. And there's some <a title="tricky research" target="_blank" href="http://clinpsyc.blogspot.com/2006/11/uh-oh-chuck-they-out-to-get-us-man_28.html" id="q8rt">tricky research</a> involving Risperdal that seemed to suggest the manipulation of the statistics was more impressive than the actual drug in treating depression. Seroquel's <a title="unimpressive efficacy" target="_blank" href="http://carlatpsychiatry.blogspot.com/2009/04/seroquel-gets-abilify-fda-treatment.html" id="dbsh">unimpressive efficacy</a> and problematic side effects are also not a ball of fun. And so forth. Isn't "progress" beautiful?<br /><br />I know what some people are thinking, so before you waste your valuable time with a comment, consider this. I'm aware that many of these patients are suffering much more than a simple case of the blues. That doesn't mean we should throw heavy duty antipsychotics at them, particularly at high doses. Certainly there has to be something else. What might that be? Some psychotherapy, some medications, some case management - I ain't saying it'll be easy. But I'm willing to bet that chucking antipsychotics at them <i>en masse</i> is not the solution.http://clinpsyc.blogspot.com/2009/07/thanks-for-your-service-now-take-this.htmlnoreply@blogger.com (CL Psych)7tag:blogger.com,1999:blog-33960805.post-5527581675571256493Wed, 15 Jul 2009 20:29:00 +00002009-07-15T13:32:02.425-07:00marketingWill Pharma's (Tax) Free Speech Be Limited?Dan Neil has an absolutely marvelous <a title="column" target="_blank" href="http://www.latimes.com/business/la-fi-ct-neil14-2009jul14,0,5977463.column" id="y85v">column</a> in the LA Times about pharma's bitching/moaning regarding increased regulation of its advertising and its potential loss of tax writeoffs associated with drug ads. It's nice to know that when I'm watching a misleading advertisement for, say, Cymbalta or Abilify, pharma is writing off the advertising cost on its tax bill. Big Pharma's legal consultants have weighed in for years on this topic, using such terms as "starkly unconstitutional," "censorship," "plainly violates the First Amendment", and adding that taking away the tax deduction is "Draconian punishment" - see <a title="this document" target="_blank" href="http://www.cohealthcom.org/content/library/articles/WLF_DrugAds_KampFriede.pdf" id="dt9s">this document</a> from the pharma-friendly Washington Legal Foundation and just try to keep a straight face. <br /><br />Neil writes that:<br /><blockquote>Currently in draft form, these [FDA] rules would dramatically raise the legal bar for risk disclosure. Not only would advertisements have to fully explicate serious side effects, the nature of adverse reactions, the risk of dependence, dangerous drug interactions and so on, but all of that would also have to be communicated in the most direct, unambiguous and, if you will, artless form possible.<br /></blockquote>And, picking some of the low-hanging fruit, Neil goes on to describe two of my most hated ads:<br /><blockquote>Consider, the current 75-second spot for Abilify, a powerful antipsychotic drug marketed as a potential add-on to antidepressants. At the 33-second mark, the warnings start: "thoughts of suicide," "elderly dementia patients . . . have an increased risk of death or stroke," "uncontrollable muscle movements [that] may become permanent" and so on. The astonishing thing is that Bristol-Myers Squibb spent more than $35 million in the first quarter alone to market this witch's brew.<br /><br />Seizures, death, trouble swallowing. Jeez, I get depressed just watching the ad. Maybe that's the idea.<br /><br />Another wonder drug -- as in, I wonder if this will kill me? -- is Wyeth's Pristiq. Again, the potential adverse reactions are alarming: "Antidepressants can increase suicidal thoughts and behaviors in children, teens and young adults," the ad says. "May cause or worsen high blood pressure, high cholesterol and glaucoma."<br /><br />Scary stuff. And yet, the FDA might say, not scary enough. Because the voice-over rambles on with a litany of potential side effects, some of which is quite hard to follow, the commercial seems to violate the FDA's constraint that advertisements not overwhelm viewers' "cognitive load." On a more prosaic level, the imagery of this suffering woman suddenly redeemed by this medication, so that now she's playing with her family at the park, seems to vastly over-promise relief.<br /></blockquote>Vastly over-promising relief, indeed. Watching Congress, the FDA, the pharma-funded academic <a href="http://carlatpsychiatry.blogspot.com/2009/07/acre-academics-craving-reimbursement.html">hired guns</a>, and lawyers on these issues will make for an entertaining spectator sport. Not nearly as engrossing as watching the DSM-V drama unfold (<a title="1" target="_blank" href="http://carlatpsychiatry.blogspot.com/2009/06/psychiatrys-dsm-v-process-now-bar-room.html" id="jgm-">1</a>, <a title="2" target="_blank" href="http://carlatpsychiatry.blogspot.com/2009/07/old-friends-battle-it-out-over-dsm-v.html" id="ktgx">2</a>, <a title="3" target="_blank" href="http://carlatpsychiatry.blogspot.com/2009/07/dsm-v-armageddon-part-2.html" id="kvj4">3</a>), but still a lot cheaper than going to a Yankees game.http://clinpsyc.blogspot.com/2009/07/will-pharmas-tax-free-speech-be-limited.htmlnoreply@blogger.com (CL Psych)1tag:blogger.com,1999:blog-33960805.post-5723325840706912137Wed, 15 Jul 2009 01:44:00 +00002009-07-14T18:50:05.407-07:00NemeroffAward Winning Journalism (?)Erroneous reporting wins prestigious award, starring Charles Nemeroff. Oy. Brought to you courtesy of<a href="http://hcrenewal.blogspot.com/2009/07/peabody-award-for-show-featuring.html"> Health Care Renewal</a>. Read the full story and shake your head. Teaser:<br /></p> <p class="Normal"></p><blockquote>Something about the simultaneously complex and sympathetic nature of mental health reporting is making reputable journalistic organizations and well-meaning reporters sloppy.</blockquote>http://clinpsyc.blogspot.com/2009/07/award-winning-journalism.htmlnoreply@blogger.com (CL Psych)0tag:blogger.com,1999:blog-33960805.post-1955730753829719664Fri, 19 Jun 2009 17:59:00 +00002009-06-19T11:00:48.455-07:00Corceptkey opinion leadermifepristoneNew American Psychiatric Association Prez: We Want MoneyIn a <a title="recent speech" target="_blank" href="http://pn.psychiatryonline.org/cgi/content/full/44/12/9?etoc" id="iwnf">recent speech</a>, incoming American Psychiatric Association president Alan Schatzberg was quoted as saying:<br /><blockquote>"As the recent attacks on APA and leaders of the profession have occurred, it has struck me that some of the detractors in the press have voiced concern that some folks have earned too good a living, often by doing presentations," he said. "I have heard from colleagues and directly from one reporter asking me about one of my colleagues having too high an annual income. I can assure you these detractors would not ask the same question of a surgeon or radiologist earning 10 times the amount paid our colleagues. <span style="color: rgb(255, 153, 0);">None of us do what we do for money</span>. Yet, it is also time for us to realize that our members and residents have never taken vows of poverty, and the complexity of the work deserves to be recognized. We need to ask ourselves how we have contributed to our own devaluation with which others seem to resonate, and we need to reverse the course. <span style="color: rgb(255, 153, 0);">The rewards for our dedication should not be limited to a sense of pride, but we are also entitled to be paid commensurate to the challenge.</span><br /></blockquote>So Schatzberg must be diving into dumpsters, begging at interstate off-ramps, and the like. Oh, wait a minute. This is the same Alan Schatzberg who in 2007 owned close to 5 million shares of Corcept (which translates into roughly 5 million dollars). I have no idea how many shares he owns currently. Corcept, in case you missed it, has shown its drug mifepristone (aka RU-486: "The Abortion Pill") is ineffective in relieving depression among patients with psychotic depression. Schatzberg, at one time, was the <a title="chief scientific officer" target="_blank" href="http://pn.psychiatryonline.org/cgi/content/full/44/12/9?etoc" id="ru3_">chief scientific officer</a> of Corcept and was also the cofounder of the company. According to Corcept's website, he is still a scientific advisor. Despite the stuides of mifepristone showing negative results, the results were spun in a manner to make them sound as if they were positive (<a title="1" target="_blank" href="http://clinpsyc.blogspot.com/2006/11/mifepristone-ru-486-move-goalposts.html" id="w7gx">1</a>, <a title="2" target="_blank" href="http://hcrenewal.blogspot.com/2006/07/conflicts-of-interest-at-stanford.html" id="b8f9">2</a>, <a title="3" target="_blank" href="http://clinpsyc.blogspot.com/2007/03/corcept-spins-out.html" id="m1yh">3</a>, <a title="4" target="_blank" href="http://hcrenewal.blogspot.com/2006/07/conflicts-of-interest-at-stanford.html" id="hndq">4</a>). In a press release, Schatzberg <a title="was quoted" target="_blank" href="http://www.latimes.com/news/opinion/web/la-oew-rubin11dec11,1,3436804.story" id="r5pe">was quoted</a> as saying that mifepristone "may be the equivalent of shock treatments in a pill." Right, with all of the negative studies, it's definitely shock treatment, meditation, and running a marathon all wrapped together in a capsule. Should he be paid "commensutate to the challenge" of trying to weave positive findings from negative results? I don't know what role, if any, he played in the misleading publications surrounding mifepristone. But in his role as chief of the scientific advisory board, I'd venture a guess that he had some involvement. But worry not, the negative results were not spun into positive findings for the sake of money, but for an altruistic love of patients with depression. I'm touched. <br /><br />Schatzberg was also busted by yours truly putting his name on a <a title="duplicate publication" target="_blank" href="http://clinpsyc.blogspot.com/2008/09/cymbalta-schatz-storm-duplicate.html" id="tx_a">duplicate publication</a> that pimped Cymbalta, Lilly's antidepressant. The study presented data from the same set of patients who were involved in a previously published Cymbalta study. Scientific results are not meant to be published in nearly identical form in two different journals. But that didn't stop Schatzberg and his coauthors. If you've not read the lengthy post on this topic, please feel free to <a title="check it out" target="_blank" href="http://clinpsyc.blogspot.com/2008/09/cymbalta-schatz-storm-duplicate.html" id="flw-">check it out</a> in order to understand my cynicism regarding his recent speech.<br /><br />Another quote from his talk:<br /><blockquote>We need to sit down with industry and come up with ways of interacting that are acceptable to both sides and fit with future guidelines. I have pledged to follow up on recent initiatives and work with Dr. Scully [APA's medical director] and our Board of Trustees to effect a new partnership—a partnership we can be proud of for what it contributes to the well-being of our patients and our profession.<br /></blockquote>I can only wonder what type of mutually agreeable interactions would meet Schatzberg's standards. Duplicate publication, serving as a scientific advisor for a company that writes scientifically dubious papers? And it appears that he's encouraging psychiatrists to be greedy -- take the money and don't feel bad about it. Taking industry money is perfectly acceptable in some instances, but it needs to be transparent, and there are plentiful examples of academics getting paid by industry and slanting science in a sponsor-friendly way. <br /><br />And the clincher:<br /><blockquote>"The time has come," he said, "to be proud of what we do and to advocate for what we and our patients justly deserve."<br /></blockquote>Right, psychiatrists deserve to make as much money as possible bending science for corporate sponsors -- and they should be proud of it too. Am I being too cynical? Maybe. But when a guy with Schatzberg's record starts talking about psychiatrists needing to rake in more money from industry, it makes me think I'm living in Bizarro World. Get ready, APA memebers; it's going to be an interesting ride.http://clinpsyc.blogspot.com/2009/06/new-american-psychiatric-association.htmlnoreply@blogger.com (CL Psych)16tag:blogger.com,1999:blog-33960805.post-7420847787116474070Fri, 12 Jun 2009 13:09:00 +00002009-06-12T06:11:20.370-07:00ghostwritingGlaxoSmithKlinekey opinion leaderZyprexaGreedy and Ghostly Scientists<img id="qlk_" style="float: left; margin-left: 0pt; margin-right: 1em; width: 331px; height: 245px;" src="http://docs.google.com/File?id=ddzsmvfh_392fghbp2db_b" /> Story one: Zachary Stowe, psychiatrist at Emory University becomes Charles Nemeroff, Jr. Read all about it the <a title="Carlat Psychiatry Blog" target="_blank" href="http://carlatpsychiatry.blogspot.com/2009/06/latest-conflict-of-interest-poster.html" id="j.jz">Carlat Psychiatry Blog</a> and <a title="University Diaries" target="_blank" href="http://www.margaretsoltan.com/?p=13846" id="ospd">University Diaries</a>. And check out the <a title="WSJ Health Blog" target="_blank" href="http://blogs.wsj.com/health/2009/06/10/another-emory-psychiatrist-draws-fire-for-payments-from-glaxo/tab/comments/" id="q:nk">WSJ Health Blog</a> as well. The gist is that Stowe apparently did not report all of his external income from his many pharmaceutical industry gigs. Better yet, he was a frequent speaker for GlaxoSmithKline, which had the gall to cancel two of his commercial talks. He then wanted GSK to pay him even though he wasn't going to give the speeches. Read the relevant emails toward the bottom of <a title="this document" target="_blank" href="http://s.wsj.net/public/resources/documents/WSJ_LttrEmoryUni_090609.pdf" id="vv3v">this document</a>. After reading about Stowe, refresh your memory about <a title="Golden Goblet" target="_blank" href="http://clinpsyc.blogspot.com/2007/04/paxil-and-pimping.html" id="ia56">Golden Goblet</a> Lifetime Achievement Award Winner, former Chair of Psychiatry at Emory University: <a title="Charles Nemeroff" target="_blank" href="http://clinpsyc.blogspot.com/2008/10/month-in-life-of-chuck-high-life.html" id="ir4a">Charles Nemeroff</a>. Is there something in the water at Emory? Or is that just how we roll in modern academic psychiatry? Stowe is hereby nominated for a coveted Golden Goblet for his string of emails in which he attempted to shake down GlaxoSmithKline. Sometimes I think that the only thing worse than drug companies are the narcissistic academics who they employ as "key opinion leaders." Not all key opinion leaders are jerks; some are probably even able to reasonably balance their industry cash with being good scientists. But Stowe didn't really portray himself as Mr. Nice Guy in his string of soon to be infamous emails.<br /><br />Oh, and this <a title="little gem" target="_blank" href="http://s.wsj.net/public/resources/documents/WSJ_LttrEmoryUni_090609.pdf" id="l6om">little gem</a>:<br /><br />"Especially disturbing is an email between employees at GSK and a public relations (PR) firm that the GSK hired. The email was titled “For your review/Paxil Breast Milk Press Release” and states:<br /><blockquote>"[P]lease review the attached press release and forward me any comments/edits.<br />As you may know, Dr. Stowe is on board for publicity efforts and NAME<br />REDACTED and I are coordinating time to meet with him next week to arm him<br />with the key messages for this announcement, which is slated for early February.<br />We are sending the release for your review at the same time in efforts to secure<br />distribution on Emory letterhead (as you know, would provide further credibility<br />to data for the media)."<br /><br />In his testimony, Dr. Stowe confirmed that the press release was written by the PR<br />firm and concerned his research on Paxil and its presence in breast milk. He also<br />explained that placing the press release on Emory letterhead, as opposed to GSK letterhead, would make the data more credible to the public."<br /></blockquote>If I have this straight, Stowe was willing to place a press release written by a PR firm hired by GSK on official university letterhead to enhance its credibility. Apparently he wasn't concerned about his own credibility. Read the full document of Senator Charles Grassley's <a title="latest investigation" target="_blank" href="http://s.wsj.net/public/resources/documents/WSJ_LttrEmoryUni_090609.pdf" id="nzi2">investigation</a> of Dr. Stowe. <br /><br /><b>Part 2: Enter the Ghostwriters</b><br /><br />One snippet, then go to <a title="Bloomberg" target="_blank" href="http://www.bloomberg.com/apps/news?pid=20601087&amp;sid=a6yFu_t9NyTY" id="ke62">Bloomberg</a> for the rest:<br /> <blockquote><p>Ensuring that medical journal articles presented Zyprexa study results in a positive light was one way for Lilly to reach its sales goal, company officials said in its plan, according to the documents. To do that, Lilly officials hired ghostwriters to prepare submissions to journals such as <a href="http://www.progressnp.com/view/0/index.html" target="_blank">Progress in Neurology and Psychiatry</a>, according to the unsealed documents. “The paper for the Progress in Neurology and Psychiatry supplement has been completed and sent to the journal for peer review,” Kerrie Mitchell, an employee of the public relations agency Cohn &amp; Wolfe, wrote in a Feb. 23, 2001, e-mail to Michael Sale, a Lilly marketing official. The message was among the unsealed files. “We ‘ghost’ wrote this article and then worked with author Dr. Haddad to work up the final copy,” Mitchell said in the e- mail. Eric Litchfield, a spokesman for Cohn &amp; Wolfe, didn’t immediately return a call requesting comment.<br /></p></blockquote> The Bloomberg story is based on a recently released set of internal Lilly documents. That's right -- more Zyprexa documents are on the loose. And the first round of documents provided some good stuff (<a title="1" target="_blank" href="http://clinpsyc.blogspot.com/2007/02/zyprexa-off-label-marketing-part-2.html" id="g6cf">1</a>, <a title="2" target="_blank" href="http://www.furiousseasons.com/archives/2007/02/the_zyprexa_chronicles_marketing_zyprexa_as_the_new_mood_stabilizer_for_bipolar_disorder_and_downpla_1.html" id="ob4q">2</a>, <a title="3" target="_blank" href="http://industry.bnet.com/pharma/10002531/eli-lilly-promoted-zyprexa-for-patients-who-were-badly-dressed" id="f28t">3</a>), so I can't wait to see what kind of chicanery will be revealed by the latest round. In one sense, it's not exactly news that Lilly ghostwrote Zyprexa papers. We all know that ghostwriting is rampant. How else do key opinion leaders get their names on dozens of papers per year when they are also flying around the country pimping drugs, holding administrative meetings, and doing all sorts of other tasks? But it's nice to have it officially documented that Lilly was playing the <a title="ghostwriting game" target="_blank" href="http://clinpsyc.blogspot.com/2006/10/osteoporosis-training-sign-up-now.html" id="y4:b">ghostwriting game</a> with Zyprexa.http://clinpsyc.blogspot.com/2009/06/greedy-and-ghostly-scientists.htmlnoreply@blogger.com (CL Psych)7tag:blogger.com,1999:blog-33960805.post-4767283385771659163Tue, 09 Jun 2009 11:17:00 +00002009-06-09T04:21:01.327-07:00AbilifyantidepressantsantipsychoticAbilify for Depression: Patients Give it an Oh-For-Three<img id="dakk" style="float: left; margin-left: 0pt; margin-right: 1em;" src="http://docs.google.com/File?id=ddzsmvfh_389f7g874g9_b" width="315" height="205" />Abilify for depression: you've seen the ads. You've hopefully read this blog (<a title="1" href="http://clinpsyc.blogspot.com/2009/03/abilify-depression-and-memory-hole.html" id="uxwr">1</a>, <a title="2" target="_blank" href="http://clinpsyc.blogspot.com/2009/05/if-youve-been-reading-about-abilify-for.html" id="n4-5">2</a>) and the excellent series in the <a title="LA Times" target="_blank" href="http://www.latimes.com/features/health/la-he-antipsychotics13-2009apr13,0,2324987.story" id="y981">LA Times</a> from Melissa Healy. The advantage over placebo is nothing to get particularly excited about. Especially from the patients' point of view. As I have mentioned previously, the two studies that were touted by <a title="key opinion leaders" target="_blank" href="http://clinpsyc.blogspot.com/2009/03/abilify-depression-and-memory-hole.html" id="hrv3">key opinion leaders</a> are supporting the efficacy of Abilify for depression suffered from a number of problems. Most germane to this post, the patient self-report rating scales did not indicate a significant advantage for Abilify in either study. <br /><br />Well, yet another Abilify for depression study is out in <a title="CNS Spectrums" target="_blank" href="http://mbldownloads.com/0409CNS_Berman.pdf" id="wt8o">CNS Spectrums</a> and guess what... Still not a significant advantage over placebo according to patients. So in each of three large studies, Abilify has failed to beat a placebo according to patients' self-report. These three trials are the basis for the massive marketing campaign and an FDA approval. Abilify started off as an also-ran antipsychotic. But times have changed. Bristol-Myers Squibb's CEO <a title="prophetically stated" target="_blank" href="http://www.news-medical.net/news/5220.aspx" id="k3hb">prophetically stated</a> in 2004 after Abilify's approval as a treatment for bipolar disorder:<br /><blockquote>This approval underscores our commitment to delivering innovative solutions that address unmet needs for a <span style="color: rgb(255, 153, 0);">broad spectrum of patients with mental illness</span>, as well as their families and health care providers. <br /></blockquote>He could as easily have stated: "This approval underscores our commitment to rebranding our unpopular antipsychotic as a Swiss Army Knife/broad spectrum psychotropic that treats everything under the sun. If I can get the FDA and the public to believe that this akathisia-inducing bottom feeder can treat depression, then I'll be LOADED, BWAAH, HA HA HA HA!!!" <br /><br />OK, maybe he didn't actually say any of those things, but his "broad spectrum" comment was literally right on the money. Just don't ask those pesky patients what they think; they might tell you it's no better than a damn sugar pill. <br /><br />Yes, I'm aware that on some other rating scales, Abilify was rated as superior to a placebo, but I'm thinking that if the patient self-report of depression is consistently not favorable for Abilify, then who are we kidding by calling it an antidepressant?<br /><br /><span style="float: left; padding: 5px;"><a href="http://www.researchblogging.org"><img alt="ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png" style="border:0;" /></a></span><br /><br /><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=CNS+Spectrums&amp;rft_id=info%3Adoi%2F&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Aripiprazole+Augmentation%0D%0Ain+Major+Depressive+Disorder%3A%0D%0AA+Double-Blind%2C+Placebo-Controlled%0D%0AStudy+in+Patients+with+Inadequate%0D%0AResponse+to+Antidepressants&amp;rft.issn=&amp;rft.date=2009&amp;rft.volume=14&amp;rft.issue=4&amp;rft.spage=197&amp;rft.epage=206&amp;rft.artnum=&amp;rft.au=Robert+M.+Berman&amp;rft.au=Maurizio+Fava&amp;rft.au=Michael+E.+Thase&amp;rft.au=Madhukar+H.+Trivedi&amp;rft.au=Ren%C3%A9+Swanink&amp;rft.au=Robert+D.+McQuade&amp;rft.au=William+H.+Carson&amp;rft.au=David+Adson&amp;rft.au=Leslie+Taylor&amp;rft.au=James+Hazel&amp;rft.au=Ronald+N.+Marcus&amp;rfe_dat=bpr3.included=1;bpr3.tags=Health%2CPsychiatry">Robert M. Berman, Maurizio Fava, Michael E. Thase, Madhukar H. Trivedi, René Swanink, Robert D. McQuade, William H. Carson, David Adson, Leslie Taylor, James Hazel, &amp; Ronald N. Marcus (2009). Aripiprazole Augmentation in Major Depressive Disorder: A Double-Blind, Placebo-Controlled Study in Patients with Inadequate Response to Antidepressants <span style="font-style: italic;">CNS Spectrums, 14</span> (4), 197-206</span>http://clinpsyc.blogspot.com/2009/06/abilify-for-depression-patients-give-it.htmlnoreply@blogger.com (CL Psych)3tag:blogger.com,1999:blog-33960805.post-740223905628006034Wed, 03 Jun 2009 12:56:00 +00002009-06-03T05:58:49.961-07:00ADHDpseudoevidence based medicinePseudoscience, Candy, and Lamar Odom: Brought to you by Daniel Amen<img id="gjyr" style="float: left; margin-left: 0pt; margin-right: 1em;" src="http://docs.google.com/File?id=ddzsmvfh_387fbxqjmdb_b" width="198" height="248" />If you follow professional basketball, you've probably noticed that LA Lakers forward Lamar Odom has a well-deserved reputation for inconsistent play. When he's good, he's close to amazing, and when he's bad, he's of little use to his team. So how is this related to mental health? Does he have social anxiety disorder? No, get out of Ricky Williams mode and pay attention...<br /><br />Odom eats candy. Lots of it. And that's why his play is inconsistent. At least that's the story according to Dr. Daniel Amen, who, according to the <a title="Los Angeles Times" target="_blank" href="http://www.latimes.com/sports/la-sp-random1-2009jun01,0,7864160.story" id="s-eh">Los Angeles Times</a> stated:<br /><blockquote>Odom freely confesses that he just can't help himself when it comes to the sweet stuff and always keeps a stash on hand of Gummi Bears, Honey Buns, Lifesavers, Hershey's white chocolate, Snickers bars, cookies and more. He eats the sugary snacks morning, noon and night, and even says he sometimes wakes up in the middle of the night, chows down on some treats, then falls back asleep.<br /><br />This is bad news for the Lakers. I've been telling my patients for years that sugar acts like a drug in the brain. It causes blood sugar levels to spike and then crash, leaving you feeling tired, irritable, foggy and stupid. Eating too much sugar impairs cognitive function, which may explain why Odom doesn't always make the smartest decisions on the court. . . .<br /><br />As a fan and a physician, it concerns me that our professional sports organizations and players are not more concerned about brain health, which includes nutrition. My advice to Odom and to all sugar addicts is to get your sugar consumption under control. You'll feel so much better and your brain will function better too. And, maybe the Lakers can get their 15th championship and Odom can get his first.<br /></blockquote> Now, remember that Odom's play is <i>inconsistent</i>, not consistently bad. And if he is eating sugar all the time, shouldn't his play be consistently poor? Oh, and is there any science at all to support the idea that eating sugar impairs athletic performance...? I'll admit to not being a top expert on this, but my brief search of PubMed did not bring up anything to support Dr. Amen's suggestions.<br /><br />So who is this Amen guy, anyway? He claims that Alzheimer's can be detected early through the use of SPECT brain imaging (single photon emission computed tomography). And <a title="he sells" target="_blank" href="http://www.amenclinics.com/store/" id="cxmu">he sells</a> vitamins/nutraceuticals on his site which, of course allegedly help to prevent cognitive deterioration. There is sooooooooo much more to read about Amen, and I encourage y'all to head over to <a title="Salon" target="_blank" href="http://www.salon.com/mwt/mind_reader/2008/05/12/daniel_amen/" id="a6xp">Salon</a> to read an excellent debunking of Amen's many pseudoscientific claims.<br /><br />I've rolled my eyes at this guy for years, but now that he's trying to shoot his witchcraft at the fine sport of basketball, I've hit my breaking point. But what do I know... I mean, Amen <a title="apparently wrote" target="_blank" href="http://www.salon.com/mwt/mind_reader/2008/05/12/daniel_amen/" id="ia0f">apparently wrote</a> that<br /><blockquote>From the first month that I started to order these (SPECT) scans, I felt that they had a special place in science and that I was led by God to pursue this work<br /></blockquote> And who am I to argue with a guy who was sent by God to practice medicine. But back to Lamar Odom; he insists that he ate <a title="candy for breakfast" target="_blank" href="http://sports.yahoo.com/nba/blog/ball_dont_lie/post/Lamar-Odom-s-sweet-tooth-is-posting-double-doubl?urn=nba,167483" id="aoj-">candy for breakfast</a> on the game days in which he played well against the Denver Nuggets. Well, maybe, but I bet a SPECT scan or two would figure out why his performance is inconsistent.<br /><br />Dr. Amen also has some hot, hot science about the men, sex, and the brain. On The View, of all places. Get ready to cringe.<br /><br /><object width="425" height="344"><param name="movie" value="http://www.youtube.com/v/nY_wOVm_An8&amp;hl=en&amp;fs=1"></param><param name="allowFullScreen" value="true"></param><param name="allowscriptaccess" value="always"></param><embed src="http://www.youtube.com/v/nY_wOVm_An8&amp;hl=en&amp;fs=1" type="application/x-shockwave-flash" allowscriptaccess="always" allowfullscreen="true" width="425" height="344"></embed></object><br /><br />OK, fine. One more. Dr. Amen can target treatment for ADHD appropriately by... yes, using pricey and unproven brain scans! See below...<br /><br /><object width="425" height="344"><param name="movie" value="http://www.youtube.com/v/zVfcu1j_A7E&amp;hl=en&amp;fs=1"></param><param name="allowFullScreen" value="true"></param><param name="allowscriptaccess" value="always"></param><embed src="http://www.youtube.com/v/zVfcu1j_A7E&amp;hl=en&amp;fs=1" type="application/x-shockwave-flash" allowscriptaccess="always" allowfullscreen="true" width="425" height="344"></embed></object>http://clinpsyc.blogspot.com/2009/06/pseudoscience-candy-and-lamar-odom.htmlnoreply@blogger.com (CL Psych)2tag:blogger.com,1999:blog-33960805.post-7201898184375066286Fri, 22 May 2009 16:58:00 +00002009-05-22T10:21:46.275-07:00Furious SeasonsSeroquelOpen Up Yer WalletsYeah, I know the economy is in very bad shape and possibly getting worse. But for the kind of fantastic investigative journalism we get from the inimitable Philip Dawdy at Furious Seasons, one really should whip out the credit card and make a donation. A summary of his good work is <a href="http://www.furiousseasons.com/archives/2009/05/summer_fundraiser_begins.html">available</a>, and his more recent work on Seroquel is worthy of accolades (<a href="http://www.furiousseasons.com/archives/2009/05/seroquel_documents_astrazeneca_exec_admits_fuckups_in_seroquel_study_published_article.html">1</a>, <a href="http://www.furiousseasons.com/archives/2009/05/seroquel_documents_az_hid_significant_seroquel_weight_gain_from_doctors_patients.html">2</a>).<br /><br />Donate <a href="http://www.furiousseasons.com/">here</a>.http://clinpsyc.blogspot.com/2009/05/open-up-yer-wallets.htmlnoreply@blogger.com (CL Psych)7tag:blogger.com,1999:blog-33960805.post-7679512249172575881Thu, 07 May 2009 17:53:00 +00002009-05-11T05:07:30.878-07:00Abilifystealth marketingPhase V, Abilify, and Vanishing Akathisia<img id="eu3y" style="float: left; margin-left: 0pt; margin-right: 1em;" src="http://docs.google.com/File?id=ddzsmvfh_385gnhwqzds_b" width="231" height="264" />If you've been reading about Abilify for depression on this site, you've probably noticed that I've been down on Abilify for causing akathisia in a frighteningly high percentage of patients. In <a title="two recent trials" target="_blank" href="http://clinpsyc.blogspot.com/2009/03/abilify-depression-and-memory-hole.html" id="xowh">two recent trials</a>, akathisia occurred in 25% of Abilify patients compared to 4% of placebo patients. What, exactly, is akathisia? That's still a matter of some debate. Let's turn to a recent <a title="Journal of Clinical Psychiatry" target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed/19389331?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" id="s0v6">Journal of Clinical Psychiatry</a> article on the topic. Entitled "Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics," the paper purports to provide "a review of the literature on the incidence of drug-induced akathisia associated with the use of second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs)."<br /><br />It provides a few different characteristics associated with acute akathisia, including:<br /><ul><li>"Intense dysphoria</li><li>Awareness of restlessness</li><li>Complex and semipurposeful motor fidgetiness"</li></ul>It mentions "...suicidal behavior has been described in patients with akathisia in case reports, both in patients receiving antipsychotic medication and in patients receiving selective serotonin reuptake inhibitors (SSRIs)."A couple of descriptions from <a title="another journal" target="_blank" href="http://medicine.plosjournals.org/perlserv/?request=get-document&amp;doi=10.1371%2Fjournal.pmed.0030372" id="ryj1">another journal</a>:<br /><ul><li>Increased tenseness, restlessness, insomnia and a feeling of being very uncomfortable</li><li>On the first day of treatment he reacted with marked anxiety and weepiness, on the second day felt so terrible with such marked panic at night that the medication was cancelled</li></ul>So we can all agree that akathisia does not sound like fun.<br /><br />Now back to the Journal of Clinical Psychiatry review article. What did the authors conclude? "The comparative incidence of akathisia among the newer antipsychotic agents remains poorly characterized." And "...SGAs are generally associated with a lower propensity for movement disorders compared with their FGA counterparts, an emerging body of comparative literature shows that second-generation medications are not completely free from inducing akathisia."<br /><br />The authors go through a long list of second-generation antipsychotic medications. The drug that receives the least attention is aripiprazole (Abilify). The authors conclude that "in studies comparing aripiprazole with placebo, akathisia rates in the aripiprazole arm were similar in some studies, and higher in others. As with other SGAs, akathisia rates with aripiprazole were lower than those of FGAs." So Abilify causes less akathisia than older medications and it's unclear if it causes more akathisia than placebo. But, wait, wasn't akathisia related to <b>much</b> higher rates of akathisia than placebo in treating depression? Fortunately, the authors had a little trick to erase that inconvenient piece of evidence; they only examined trials trials involving people diagnosed with schizophrenia or bipolar disorder. So the depressio<img id="tnfa" style="width: 320px; height: 294px; float: right; margin-left: 1em; margin-right: 0pt;" src="http://docs.google.com/File?id=ddzsmvfh_384d3ngfgfc_b" />n studies -- POOF -- vanished, along with their damning data.<br /><br />Why would the authors want to censor negative data about Abilify? Well, one author is an employee of Otsuka America Pharmaceutical, Inc., and another is an employee of Bristol-Myers Squibb, companies that market Abilify. And the other authors: All but one of them have a financial relationship with Bristol-Myers Squibb. The best part:<br /><blockquote>Editorial support provided by Maria Soushko, Ph.D., Phase Five Communications, Inc., New York, N.Y., with funding provided by Bristol-Myers Squibb.</blockquote>So a paper that excludes the most inconvenient evidence regarding akathisia on Abilify had major parts of the writing done by... a medical writer hired by Bristol-Myers Squibb. If one goes to Phase Five's <a title="website" target="_blank" href="http://www.phase-five.com/" id="uy1z">website</a> , the first animation that pops up says "Spinning Your Science Into Gold." I'd say that this article was indeed 24 karat gold. I hereby nominate all authors of the study for a much coveted <a title="Golden Goblet" target="_blank" href="http://clinpsyc.blogspot.com/2007/04/paxil-and-pimping.html" id="uv9y">Golden Goblet</a> Award.<br /><br /><br /><span style="padding: 5px; float: left;"><a href="http://www.researchblogging.org/"><img alt="ResearchBlogging.org" src="http://www.researchblogging.org/public/citation_icons/rb2_large_gray.png" style="border: 0pt none ;" /></a></span><br /><br />Citation Below:<br /><br /><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.jtitle=The+Journal+of+Clinical+Psychiatry&amp;rft_id=info%3Adoi%2F10.4088%2FJCP.08r04210&amp;rfr_id=info%3Asid%2Fresearchblogging.org&amp;rft.atitle=Akathisia%3A+An+Updated+Review+Focusing+on+Second-Generation+Antipsychotics&amp;rft.issn=1555-2101&amp;rft.date=2009&amp;rft.volume=&amp;rft.issue=&amp;rft.spage=0&amp;rft.epage=0&amp;rft.artnum=http%3A%2F%2Fwww.psychiatrist.com%2Fabstracts%2Fabstracts.asp%3Fabstract%3Doap%2F08r04210.htm&amp;rft.au=Kane%2C+J.&amp;rft.au=Fleischhacker%2C+W.&amp;rft.au=Hansen%2C+L.&amp;rft.au=Perlis%2C+R.&amp;rft.au=Pikalov%2C+A.&amp;rft.au=Assun%C3%A7%C3%A3o-Talbott%2C+S.&amp;rfe_dat=bpr3.included=1;bpr3.tags=Health%2CPsychiatry">Kane, J., Fleischhacker, W., Hansen, L., Perlis, R., Pikalov, A., &amp; Assunção-Talbott, S. (2009). Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics <span style="font-style: italic;">The Journal of Clinical Psychiatry</span> DOI: <a rev="review" href="http://dx.doi.org/10.4088/JCP.08r04210">10.4088/JCP.08r04210</a><br /><br /><span style="font-weight: bold;">Update:</span> See a related post at the <a href="http://carlatpsychiatry.blogspot.com/2009/05/abilify-journal-of-clnical-psychiatry.html">Carlat Psychiatry Blog</a>. A partial quote:<br /></span><span style="color: rgb(0, 0, 0);"></span><blockquote><span style="color: rgb(0, 0, 0);">Publishing an article that was carefully crafted to draw attention away from Abilify's main liability was shameful, and is exactly the kind of deceptive editorial practice that we as a society can no longer tolerate.</span></blockquote>http://clinpsyc.blogspot.com/2009/05/if-youve-been-reading-about-abilify-for.htmlnoreply@blogger.com (CL Psych)8tag:blogger.com,1999:blog-33960805.post-7077188759613563658Wed, 29 Apr 2009 12:45:00 +00002009-04-29T05:46:31.050-07:00Abilifyantidepressantsantipsychoticdepressionstealth marketingAbilify Runs Amok, Runs Stealth Safety Campaign in Medical Journal<a title="Furious Seasons" target="_blank" href="http://www.furiousseasons.com/archives/2009/04/10_percent_of_depressed_patients_now_take_antipsychotics_1.html" id="jfhv">Furious Seasons</a> has a rather distressing piece of news from a recent Bristol-Myers Squibb <a title="conference call" target="_blank" href="http://seekingalpha.com/article/133733-bristol-myers-squibb-company-q1-2009-earnings-call-transcript?page=-1" id="c8zl">conference call</a>. To sum it up quickly, BMS claims that 10.6% of depressed patients are now receiving atypical antipsychotics. Of those 10.6%, 21.7% are taking Abilify. So that would mean roughly 10-11 in 100 depressed patients are taking antipsychotics and 2 of them are on Abilify. I shudder to think how many are on Seroquel. Or Zyprexa. It made me think of a <a title="prior post" target="_blank" href="http://clinpsyc.blogspot.com/2009/04/abilify-marketing-blitz-atypical.html" id="dvya">post</a> I wrote a few weeks ago in which I described the marketing of Abilify for depression. A huge market of depressed people just ripe for the picking.<br /><br />Going along with this, BMS is pushing back on the issue of akathisa, the side effect that has garnered the drug much bad publicity (at least in the blog world; <a title="1" target="_blank" href="http://clinpsyc.blogspot.com/2009/03/abilify-depression-and-memory-hole.html" id="u:ys">1</a>, <a title="2" target="_blank" href="http://www.beforeyoutakethatpill.com/2008/11/abilify-me.html" id="bdy3">2</a>, <a title="3" target="_blank" href="http://www.furiousseasons.com/archives/2008/11/abilify_is_likelier_to_cause_akathisia_than_treat_depession.html" id="l_ns">3</a>) via a medical journal article that distracts attention from Abilify as an akathisia-inducer. More on that to come soon. Ghostwriters, ignoring contradictory evidence; basically, an attempt to completely obscure the evidence on the topic. It's not the first time BMS has successfully placed a study with major flaws into a medical journal (<a title="1" target="_blank" href="http://clinpsyc.blogspot.com/2009/01/abilify-for-depression-im-not-only.html" id="ikc-">1</a>, <a title="2" target="_blank" href="http://clinpsyc.blogspot.com/2007/11/latest-abilify-for-alzheimers-study-is.html" id="t_sc">2</a>). Details will be forthcoming.http://clinpsyc.blogspot.com/2009/04/abilify-runs-amok-runs-stealth-safety.htmlnoreply@blogger.com (CL Psych)15